NCBI Conserved Domain Search

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the synaptotagmin family, mostly plants; The synaptotagmin family includes Arabidopsis thaliana synaptotagmins (AtSYT1-5) and similar proteins. AtSYT1, also called NTMC2T1.1, or synaptotagmin A (SYTA), plays an important role in maintaining plasma membrane integrity during freezing and osmotic stresses. It may function in membrane resealing during calcium-dependent freezing tolerance. It regulates endocytosis and endosome recycling at the plasma membrane and cell-to-cell trafficking of cabbage leaf curl virus (CaLCuV) and tobacco mosaic virus (TMV) movement proteins via plasmodesmata. AtSYT2, also called NTMC2T1.2, or synaptotagmin B (SYTB), may play an important role in regulating an unconventional protein trafficking from the cytosol to the extracellular matrix. AtSYT3 (also called NTMC2T1.3, or synaptotagmin C, or SYTC), AtSYT4 (also called NTMC2T2.2, or synaptotagmin D, or SYTD) and AtSYT5 (also called NTMC2T2.1, or synaptotagmin E, or SYTE) may also be involved in membrane trafficking. This model corresponds to the SMP domain of SYT family proteins, which may be implicated in lipid transport.

Pssm-ID: 439233 Cd Length: 189 Bit Score: 265.18 E-value: 3.54e-86

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  60 PSWVVFSNRQKLTWLNSHLTKIWPYVNEAASELIKTSAEPILEEYRPMILSALKFSKFTLGTVAPQFTGVSIIEDGGDGV 139
Cdd:cd21677    1 PSWVKFPDYERVDWLNKLLEKLWPYLDKAASKLVKESVEPLLEQYKPSFISSIKFKKLTLGTVPPRIEGVKVVESDEDEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 140 TMELEVQWDGNPSIILDIKTLVGLALPVQVKNVGFTGVFRLIFKPLVNEFPGFGAVCYSLRQKKKLDFTLKVIGGDISTI 219
Cdd:cd21677   81 ILDVDFRWAGDPDIVLAVKLLPGLSLPVQVKDLQLSGTVRITLKPLVDELPCFGAVSVSLVEKPVVDFDLKLLGGDDMAL 160

                        170       180
                 ....*....|....*....|....*....
gi 357478297 220 PGLYDAIEGAIRDAVEDSITWPVRKIVPI 248
Cdd:cd21677  161 PGLKSWLDSFIRDALLDMLVWPKRIVIPI 189

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 139.89 E-value: 1.34e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297   71 LTWLNSHLTKIWPYVNEAASELIKTSAEPILEEYRPMILSALKFSKFTLGTVAPQFTGV-SIIEDGGDGVTMEL------ 143
Cdd:COG5038   223 VEWLNTFLQKFWPIIEPSISQQVVDQVNQQLAEAIPSFIDALALDEFTLGSKPPRIDGIrSYPSTESDTVVMDVdfsftp 302

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  144 ---------EVQWDGNPSIILDI---KTLVGLALPVQVKNVGFTGVFRLIFKpLVNEFPGFGAVCYSLRQKKKLDFTLKV 211
Cdd:COG5038   303 hdisdvtatSARASVNPKISLVVkkgKSFGSFTLPILVEDLFFKGRVRVRVE-LMSKYPFIKTVSFQLLEVPEFDFILVP 381

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  212 IGG-----DISTIPGLYDAIEGAIRDAVEDSITWPvrKIVPI-LPGDYSDLELKPVGILEVKLVQAKELTNKDII--GKS 283
Cdd:COG5038   382 LGGdffgvDIFAIPGLSRFIQEIINSTLGPMLLPP--NSLTIdISQIMAGDSGTAIGVVEVKIKSAEGLKKSDSTinGTV 459

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  284 DPYAVLyirPLRNRTK-KSKTINNDLNPIWNEHFeFIVEDASTQHLFVKVYDDEGLQSSELIGCTDIKLSELEPGKIKDV 362
Cdd:COG5038   460 DPYITV---TFSDRVIgKTRVKKNTLNPVWNETF-YILLNSFTDPLNLSLYDFNSFKSDKVVGSTQLDLALLHQNPVKKN 535

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  363 WLklvkdLEIQRDNKNRGQVHLELLYCPYGTENsftnpfarnysmtsleKVLKGSsngidsngneseaaQRKKEVIIRGV 442
Cdd:COG5038   536 EL-----YEFLRNTKNVGRLTYDLRFFPVIEDK----------------KELKGS--------------VEPLEDSNTGI 580

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 357478297  443 LSVTVISAEDLPAVDFMGKSDPFVVLTLKKAETKNKTRVVNNslNPVWNQTFDFVVEDG 501
Cdd:COG5038   581 LKVTLREVKALDELSSKKDNKSAELYTNAKEVYSTGKLKFTN--HPSWNLQYNVLVTDR 637

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 119.35 E-value: 3.50e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTLKKAETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGKD- 519
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDd 80

                          90       100
                  ....*....|....*....|....
gi 357478297  520 YMGRVILTLTRAILEGEYKERFEL 543
Cdd:pfam00168  81 FIGEVRIPLSELDSGEGLDGWYPL 104

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain of the extended synaptotagmin (E-Syt) family; The extended synaptotagmin (E-Syt) family includes a group of Ca2+-regulated intrinsic membrane proteins, such as E-Syt1, E-Syt2 and E-Syt3. They are composed of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and five (E-Syt1) or three C-terminal cytoplasmic C2-domains (E-Syt2 and E-Syt3). The ER-membrane anchor and C2 domains are required for tethering, while the SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell. This model corresponds to the SMP domain, which has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain.

Pssm-ID: 439226 Cd Length: 177 Bit Score: 119.20 E-value: 4.02e-31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  73 WLNSHLTKIWPYVNEAASELIKTSAEPILEEYRPMILSALKFSKFTLGTVAPQFTGVSIIED--GGDGVTMELEVQWDGN 150
Cdd:cd21670    5 WLNKIIKQLWPYINEYVEKLLKEKIEPSIRALLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDnvDRDEIILDLDISYDGD 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 151 PSIILDIKTLvglaLPVQVKNVGFTGVFRLIFKPLVNEFPGFGAVCYSLRQKKKLDFTLKVIgGDISTIPGLYDAIEGAI 230
Cdd:cd21670   85 ADIEVSVGTG----IKAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGL-ANLLDIPGLSNLLRKII 159

                        170
                 ....*....|....*...
gi 357478297 231 RDAVEDSITWPVRKIVPI 248
Cdd:cd21670  160 VDQIASFLVLPNRITIPL 177

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 110.49 E-value: 6.23e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  262 GILEVKLVQAKELTNKDIIGKSDPYAVLYIRPlRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSS 341
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLD-GKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*
gi 357478297  342 ELIGCTDIKLSELEPGKIKDVWLKL 366
Cdd:pfam00168  80 DFIGEVRIPLSELDSGEGLDGWYPL 104

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the tricalbin (TCB) family; The tricalbin (TCB) family includes Saccharomyces cerevisiae TCB1-3 and similar proteins. They may play a role in membrane trafficking. This model corresponds to the SMP domain of TCB family proteins, which may be implicated in lipid transport.

Pssm-ID: 439234 Cd Length: 203 Bit Score: 109.57 E-value: 1.75e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  70 KLTWLNSHLTKIWPYVNEAASELIKTSAEPILEEYRPMILSALKFSKFTLGTVAPQFTGVSIIEDGGDG-VTMELEV--- 145
Cdd:cd21678    2 SVEWLNYFLQKFWLIYEPVLSETIVTNVNPVLAENCPSFLDSLRLTEFTLGTKAPRIEGVRTYPKTEDDvVVMDWEFsft 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 146 --------------QWdgNPSIILDI---KTLVGLALPVQVKNVGFTGVFRLIFKpLVNEFPGFGAVCYSLRQKKKLDFT 208
Cdd:cd21678   82 pndtsdltakqiknKV--NPKIVLTArvgKGVVGIDLPILVEDLSFSGKLRVRLK-LMPDFPHIKTVEVSFLEPPEIDFV 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 357478297 209 LKVIGG--DISTIPGLYDAIEGAIRDAVEDSITWPVRKIVPI 248
Cdd:cd21678  159 LKPLGGgfDIMDIPGLSTFIRSIIHSILGPMMYAPNSFTLDL 200

C2 domain; 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: 175973 [Multi-domain] Cd Length: 102 Bit Score: 105.23 E-value: 4.78e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTLKKaETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGKD-YM 521
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGG-KQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDdFL 79

                         90
                 ....*....|....*....
gi 357478297 522 GRVILTLTRAILEGEYKER 540
Cdd:cd00030   80 GEVEIPLSELLDSGKEGEL 98

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 102.18 E-value: 4.25e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297   263 ILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSE 342
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90       100
                   ....*....|....*....|.
gi 357478297   343 LIGCTDIKLSELEPGKIKDVW 363
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHEKL 101

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 102.18 E-value: 5.54e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297   442 VLSVTVISAEDLPAVDFMGKSDPFVVLTLKKAETKN-KTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGKD- 519
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKkKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDd 80

                           90
                   ....*....|....*....
gi 357478297   520 YMGRVILTLTRAILEGEYK 538
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHE 99

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP domain is a lipid transport domain found in phospholipid transfer proteins such as synaptotagmin family proteins, tricalbin (TCB) family proteins, maintenance of mitochondrial morphology protein 1 (MMM1), mitochondrial distribution and morphology protein 12 (MDM12), mitochondrial distribution and morphology protein 34 (MDM34), PDZ domain-containing protein 8 (PDZD8), testis-expressed protein 2 (TEX2), meiotically up-regulated gene 190 protein (Mug190), C2 domain-containing protein 2 (C2CD2) and C2 domain-containing protein 2-like (C2CD2L). The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP (tubular lipid-binding proteins). It adopts a TULIP fold with two alpha helices and a highly curved antiparallel beta sheet forming a cornucopia-like structure.

Pssm-ID: 439225 Cd Length: 165 Bit Score: 103.94 E-value: 7.98e-26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  90 SELIKTSAEPILEE-YRPMILSALKFSKFTLGTVAPQFTGVSIIE--DGGDGVTMELEVQWDGNPSIILDIK---TLVGL 163
Cdd:cd21669    2 EQLIRESLQELLEEvKKPSFIESLELTEFTLGSNPPRIKSVRVLDspSSDLQLVLDLDLEYAGDFSVVLSAKlggGGLGL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 164 ALPVQVKNVGFTGVFRLIFKpLVNEFPGFGAVCYSLRQKKKLDFTLKVIGG-DISTIPGLYDAIEGAIRDAVEDSITWPV 242
Cdd:cd21669   82 PVPVSVSDLSLEGRLRVRLT-LLPEFPYVGALSISFVEPPDIDFSIRPLGGvDLMELPGLSSWLEKLLTDALVELLVEPN 160


                 ....*
gi 357478297 243 RKIVP 247
Cdd:cd21669  161 RIVID 165

C2 domain; 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: 175973 [Multi-domain] Cd Length: 102 Bit Score: 101.76 E-value: 8.01e-26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPlrNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSEL 343
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGG--KQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDF 78

                         90       100
                 ....*....|....*....|....
gi 357478297 344 IGCTDIKLSELE-PGKIKDVWLKL 366
Cdd:cd00030   79 LGEVEIPLSELLdSGKEGELWLPL 102

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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 either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 100.83 E-value: 2.76e-25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDII------GKSDPYAVLYIRplrNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDD 335
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRVG---AQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDE 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 357478297 336 EGLQSSELiGCTDIKLSELEPGKIKDVWLKLvkdleiqrDNKNRGQVHLEL 386
Cdd:cd08391   78 DPDKDDFL-GRLSIDLGSVEKKGFIDEWLPL--------EDVKSGRLHLKL 119

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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 either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 93.90 E-value: 8.41e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFM------GKSDPFVVLTLkkAETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHD 514
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRV--GAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDED 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 357478297 515 TFGKDYMGRVILTLTRAILEGEYKERFELDGAKSGFLNLHLKW 557
Cdd:cd08391   79 PDKDDFLGRLSIDLGSVEKKGFIDEWLPLEDVKSGRLHLKLEW 121

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (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: 176003 [Multi-domain] Cd Length: 145 Bit Score: 88.54 E-value: 1.15e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 440 RGVLSVTVISAEDLPAVDFMGkSDPFVVLTLkkAETKNKTRVVNNSLNPVWNQTFDFVVEDgLHDMLLVEVYDHDTFGKD 519
Cdd:cd04038    1 LGLLKVRVVRGTNLAVRDFTS-SDPYVVLTL--GNQKVKTRVIKKNLNPVWNEELTLSVPN-PMAPLKLEVFDKDTFSKD 76

                         90
                 ....*....|.
gi 357478297 520 -YMGRVILTLT 529
Cdd:cd04038   77 dSMGEAEIDLE 87

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 86.20 E-value: 3.60e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTLKKAetKNKTRVVNNSLNPVWNQTFDFVVEDgLHDMLLVEVYDHDTFGK-D 519
Cdd:cd08377    1 GFLQVKVIRASGLAAADIGGKSDPFCVLELVNA--RLQTHTIYKTLNPEWNKIFTFPIKD-IHDVLEVTVYDEDKDKKpE 77

                         90
                 ....*....|....*....
gi 357478297 520 YMGRVILTLTRaILEGEYK 538
Cdd:cd08377   78 FLGKVAIPLLS-IKNGERK 95

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 175990 [Multi-domain] Cd Length: 128 Bit Score: 82.09 E-value: 1.17e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDI--IGKSDPYAVLYIRPLRNRTKkskTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQ 339
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRsgKGKSDPYAILSVGAQRFKTQ---TIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFA 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 357478297 340 SSELIGCTDIKLSELEPGKIKDV---WLKLvKDLEIQRDNKNRGQVHLEL 386
Cdd:cd04024   78 GKDYLGEFDIALEEVFADGKTGQsdkWITL-KSTRPGKTSVVSGEIHLQF 126

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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 fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 81.08 E-value: 2.22e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTLK-----KAETKNKTrvvnnsLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFG 517
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLNgekvfKTKTIKKT------LNPVWNESFEVPVPSRVRAVLKVEVYDWDRGG 74

                         90       100       110
                 ....*....|....*....|....*....|...
gi 357478297 518 K-DYMGRVILTLTRAILEGEYKERFELDGAKSG 549
Cdd:cd04040   75 KdDLLGSAYIDLSDLEPEETTELTLPLDGQGGG 107

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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.

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 78.86 E-value: 1.56e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRplrNRT-KKSKTINNDLNPIWNEHFEFIVEDAsTQHLFVKVYD-DEGLQsS 341
Cdd:cd04042    2 LDIHLKEGRNLAARDRGGTSDPYVKFKYG---GKTvYKSKTIYKNLNPVWDEKFTLPIEDV-TQPLYIKVFDyDRGLT-D 76

                         90       100
                 ....*....|....*....|....*.
gi 357478297 342 ELIGCTDIKLSELEPGKIKDVWLKLV 367
Cdd:cd04042   77 DFMGSAFVDLSTLELNKPTEVKLKLE 102

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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.

Pssm-ID: 176009 [Multi-domain] Cd Length: 124 Bit Score: 78.75 E-value: 1.58e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKS-DPFVVLTLKKAETKNKTRVVNNSLNPVWNQTFdFVVEDGLHDMLLVEVYDHDTFGKD 519
Cdd:cd04044    2 GVLAVTIKSARGLKGSDIIGGTvDPYVTFSISNRRELARTKVKKDTSNPVWNETK-YILVNSLTEPLNLTVYDFNDKRKD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 357478297 520 -YMGRVILTL----TRAILEGEYKErFELDGAKSGFLNLHLKWMP 559
Cdd:cd04044   81 kLIGTAEFDLssllQNPEQENLTKN-LLRNGKPVGELNYDLRFFP 124

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 175990 [Multi-domain] Cd Length: 128 Bit Score: 78.23 E-value: 2.70e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFM--GKSDPFVVLTLkkAETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTF-G 517
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRSgkGKSDPYAILSV--GAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFaG 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 357478297 518 KDYMGRVILTLTRAILEGE----------YKERFELDGAKSGFLNLHLKW 557
Cdd:cd04024   79 KDYLGEFDIALEEVFADGKtgqsdkwitlKSTRPGKTSVVSGEIHLQFSW 128

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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 here have a type-I topology.

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 77.30 E-value: 6.76e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 438 IIRGVLSVTVISAEDLPAVDFMGKSDPFVVLTL---KKAETKNKTRVVNNSLNPVWNQTFDFVVEDGLHD-MLLVEVYDH 513
Cdd:cd04026   10 VKDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLipdPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKDrRLSIEVWDW 89

                         90       100
                 ....*....|....*....|....*....
gi 357478297 514 DTFGK-DYMGRV---ILTLTRAILEGEYK 538
Cdd:cd04026   90 DRTTRnDFMGSLsfgVSELIKMPVDGWYK 118

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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 fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 76.45 E-value: 9.02e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIrplrNRTK--KSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYD-DEGlQS 340
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYL----NGEKvfKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDwDRG-GK 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 357478297 341 SELIGCTDIKLSELEPGKIKDVWLKLVKDleiqrDNKNRGQVHL 384
Cdd:cd04040   76 DDLLGSAYIDLSDLEPEETTELTLPLDGQ-----GGGKLGAVFL 114

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 76.18 E-value: 1.03e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDIIGKSDPYAVLyirPLRNRTKKSKTINNDLNPIWNEHFEFIVEDAsTQHLFVKVYDDEGLQSS 341
Cdd:cd08377    1 GFLQVKVIRASGLAAADIGGKSDPFCVL---ELVNARLQTHTIYKTLNPEWNKIFTFPIKDI-HDVLEVTVYDEDKDKKP 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 357478297 342 ELIGCTDIKLSELEPGKIKdvWLKLvKDLEIQRDNKnrGQVHLELLY 388
Cdd:cd08377   77 EFLGKVAIPLLSIKNGERK--WYAL-KDKKLRTRAK--GSILLEMDV 118

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 76.08 E-value: 1.66e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTL----KKAETKnKTRVVNNSLNPVWNQTFDF-VVEDGLHDM-LLVEVYDHDTF 516
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPYVKVSLlqggKKLKKK-KTSVKKGTLNPVFNEAFSFdVPAEQLEEVsLVITVVDKDSV 94

                         90
                 ....*....|.
gi 357478297 517 GKD-YMGRVIL 526
Cdd:cd00276   95 GRNeVIGQVVL 105

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176031 [Multi-domain] Cd Length: 124 Bit Score: 75.76 E-value: 1.96e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTL-----KKAETKnktrVVNNSLNPVWNQTFDF-VVEDGLHD-MLLVEVYDHDT 515
Cdd:cd08385   18 LTVGIIQAADLPAMDMGGTSDPYVKVYLlpdkkKKFETK----VHRKTLNPVFNETFTFkVPYSELGNkTLVFSVYDFDR 93

                         90
                 ....*....|....
gi 357478297 516 FGK-DYMGRVILTL 528
Cdd:cd08385   94 FSKhDLIGEVRVPL 107

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. 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 of this cd have a type-II topology.

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 75.38 E-value: 2.07e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 442 VLSVTVISAEDLPAVDFMGKSDPFVVLTLKKA-ETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGKDY 520
Cdd:cd04036    1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTAsDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMDDH 80


                 ....
gi 357478297 521 MGRV 524
Cdd:cd04036   81 LGTV 84

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. 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 of this cd have a type-II topology.

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 74.61 E-value: 4.24e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSEL 343
Cdd:cd04036    2 LTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMDDHL 81

                         90       100
                 ....*....|....*....|...
gi 357478297 344 iGCTDIKLSELEPGKIKDVWLKL 366
Cdd:cd04036   82 -GTVLFDVSKLKLGEKVRVTFSL 103

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.

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 74.33 E-value: 1.26e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 257 ELKPVGILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNR--------------------------TKKSKTINNDLNP 310
Cdd:cd08676   23 AEPPIFVLKVTVIEAKGLLAKDVNGFSDPYCMLGIVPASRErnsekskkrkshrkkavlkdtvpaksIKVTEVKPQTLNP 102

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 357478297 311 IWNEHFEFIVEDASTQHLFVKVYD--DEGLqsseliGCTDIKLSELEPGKIkDVWLKL 366
Cdd:cd08676  103 VWNETFRFEVEDVSNDQLHLDIWDhdDDFL------GCVNIPLKDLPSCGL-DSWFKL 153

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). 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 here have a type-I topology and do not bind Ca2+.

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 72.67 E-value: 2.51e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTL---KKAETKNKTRVVNNSLNPVWNQTFDF--VVEDGLHDMLL-VEVYDHDTF 516
Cdd:cd04031   18 LIVTVLQARDLPPRDDGSLRNPYVKVYLlpdRSEKSKRRTKTVKKTLNPEWNQTFEYsnVRRETLKERTLeVTVWDYDRD 97

                         90       100
                 ....*....|....*....|.
gi 357478297 517 GK-DYMGRVILTLTRAILEGE 536
Cdd:cd04031   98 GEnDFLGEVVIDLADALLDDE 118

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-2 (E-Syt2) and similar proteins; Extended synaptotagmin-2 (E-Syt2), also called Chr2Syt, tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. It binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. E-Syt2 plays a role in fibroblast growth factor (FGF) signaling via its role in the rapid internalization of FGFreceptor 1 (FGFR1) that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. E-Syt2 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and three C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to SMP domain.

Pssm-ID: 439236 Cd Length: 179 Bit Score: 73.38 E-value: 4.73e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  69 QKLTWLNSHLTKIWPYVNEAASELIKTSAEPILEEYRPMiLSALKFSKFTLGTVAPQFTGVSIIEDGGDG--VTMELEVQ 146
Cdd:cd21680    3 ERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANAH-LSTFSFTKIDLGDQPLRINGVKVYTENVDKrqIILDLQIS 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 147 WDGNPSIILDIKTLVGLAlpvQVKNVGFTGVFRLIFKPLVNEFPGFGAVCYSLRQKKKLDFTLKVIgGDISTIPGLYDAI 226
Cdd:cd21680   82 FVGNCEIDLEIKRYFCRA---GVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGL-TNLLDIPGLNGLS 157

                        170       180
                 ....*....|....*....|..
gi 357478297 227 EGAIRDAVEDSITWPVRKIVPI 248
Cdd:cd21680  158 DTIILDIISNYLVLPNRITVPL 179

C2 domain second 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175976 [Multi-domain] Cd Length: 133 Bit Score: 71.50 E-value: 6.36e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 442 VLSVTVISAEDLPAVDFMGKSDPFVVLTLK-----KAETKNKTRVVNNSLNPVWNQTFDFVV--EDGLHD--MLLVEVYD 512
Cdd:cd04009   17 SLRVEILNARNLLPLDSNGSSDPFVKVELLprhlfPDVPTPKTQVKKKTLFPLFDESFEFNVppEQCSVEgaLLLFTVKD 96

                         90
                 ....*....|....*..
gi 357478297 513 HDTFGK-DYMGRVILTL 528
Cdd:cd04009   97 YDLLGSnDFEGEAFLPL 113

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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-I topology.

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 72.36 E-value: 8.24e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 433 RKKEVIIRGVLSVTVISAEDLPAVDFMGKSDPFV---VLTLKKAETKNKTRVVNNSLNPVWNQTF---DFVVEDgLHDML 506
Cdd:cd04020   19 LKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVkcyLLPDKSKKSKQKTPVVKKSVNPVWNHTFvydGVSPED-LSQAC 97

                         90
                 ....*....|....
gi 357478297 507 L-VEVYDHDTFGKD 519
Cdd:cd04020   98 LeLTVWDHDKLSSN 111

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 70.90 E-value: 9.06e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 259 KPVGILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTINNDLNPIWNEHFEFIV--EDASTQHLFVKVYDDE 336
Cdd:cd08387   13 KDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNTKQSKIHKKTLNPEFDESFVFEVppQELPKRTLEVLLYDFD 92

                         90       100       110
                 ....*....|....*....|....*....|
gi 357478297 337 GLQSSELIGCTDIKLSELEPGKIKDVWLKL 366
Cdd:cd08387   93 QFSRDECIGVVELPLAEVDLSEKLDLWRKI 122

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. 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-II topology.

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 69.28 E-value: 3.23e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDIIGKSDPYAVLYirpLRNRTKKSKTINND-LNPIWNEHFEFIVEDAS---TQHLFVKVYDDEG 337
Cdd:cd04049    1 GTLEVLLISAKGLQDTDFLGKIDPYVIIQ---CRTQERKSKVAKGDgRNPEWNEKFKFTVEYPGwggDTKLILRIMDKDN 77

                         90
                 ....*....|....*..
gi 357478297 338 LQSSELIGCTDIKLSEL 354
Cdd:cd04049   78 FSDDDFIGEATIHLKGL 94

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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.

Pssm-ID: 176009 [Multi-domain] Cd Length: 124 Bit Score: 69.51 E-value: 3.25e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 261 VGILEVKLVQAKELTNKDIIGKS-DPYAVLYIRpLRNRTKKSKTINNDLNPIWNEHFEFIVeDASTQHLFVKVYDDEGLQ 339
Cdd:cd04044    1 IGVLAVTIKSARGLKGSDIIGGTvDPYVTFSIS-NRRELARTKVKKDTSNPVWNETKYILV-NSLTEPLNLTVYDFNDKR 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 357478297 340 SSELIGCTDIKLSEL-EPGKIKDVwlklvkDLEIQRDNKNRGQVHLELLYCP 390
Cdd:cd04044   79 KDKLIGTAEFDLSSLlQNPEQENL------TKNLLRNGKPVGELNYDLRFFP 124

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.

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 69.71 E-value: 4.94e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 442 VLSVTVISAEDLPAVDFMGKSDPFVVL----------------------------TLKKAETKNkTRVVNNSLNPVWNQT 493
Cdd:cd08676   29 VLKVTVIEAKGLLAKDVNGFSDPYCMLgivpasrernsekskkrkshrkkavlkdTVPAKSIKV-TEVKPQTLNPVWNET 107

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 357478297 494 FDFVVEDGLHDMLLVEVYDHDtfgKDYMGRVILTLTRAILEGE 536
Cdd:cd08676  108 FRFEVEDVSNDQLHLDIWDHD---DDFLGCVNIPLKDLPSCGL 147

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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.

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 68.44 E-value: 5.52e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 263 ILEVKLVQAKELTNKDIIGKSDPYAVLyirPLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSE 342
Cdd:cd08376    1 VVTIVLVEGKNLPPMDDNGLSDPYVKF---RLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDE 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 357478297 343 LIGCTDIKLSELEPGKIKDVWLKLvkdleiqrdNKNRGQVHL 384
Cdd:cd08376   78 FIGRCEIDLSALPREQTHSLELEL---------EDGEGSLLL 110

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. 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 synaptotagmin1. 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: 176063 [Multi-domain] Cd Length: 118 Bit Score: 68.43 E-value: 6.13e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLrnrTKKSKTI-NNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEgLQS 340
Cdd:cd08681    1 GTLVVVVLKARNLPNKRKLDKQDPYCVLRIGGV---TKKTKTDfRGGQHPEWDEELRFEITEDKKPILKVAVFDDD-KRK 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 357478297 341 SELIGCTDIKLSELEPGKIKDVWlklvkdLEIQRDNKNRGQVHLELLY 388
Cdd:cd08681   77 PDLIGDTEVDLSPALKEGEFDDW------YELTLKGRYAGEVYLELTF 118

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 68.60 E-value: 8.11e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTL----KKAEtKNKTRVVNNSLNPVWNQTFDFVVE-DGLHDM-LLVEVYDHD 514
Cdd:cd08405   15 NRITVNIIKARNLKAMDINGTSDPYVKVWLmykdKRVE-KKKTVIKKRTLNPVFNESFIFNIPlERLRETtLIITVMDKD 93

                         90
                 ....*....|...
gi 357478297 515 TFGK-DYMGRVIL 526
Cdd:cd08405   94 RLSRnDLIGKIYL 106

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175996 [Multi-domain] Cd Length: 127 Bit Score: 67.68 E-value: 1.32e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 428 SEAAQRKKeviirgvLSVTVISAEDLPAVDFMGKSDPFV---VLTLKKAETKNKTRVVNNSLNPVWNQTFDFVV--EDGL 502
Cdd:cd04030   10 RYSSQRQK-------LIVTVHKCRNLPPCDSSDIPDPYVrlyLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVslEELK 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 357478297 503 HDMLLVEVYDHDTF---GKDYMGRVILTLTRAILEGEYKERFEL 543
Cdd:cd04030   83 RRTLDVAVKNSKSFlsrEKKLLGQVLIDLSDLDLSKGFTQWYDL 126

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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.

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 67.36 E-value: 1.50e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTLKkaETKNKTRVVNNSLNPVWNQTFDFVVEDG---LHDMLLVEVYDH--DTFG 517
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELDFD--GQKKRTRTKPKDLNPVWNEKLVFNVSDPsrlSNLVLEVYVYNDrrSGRR 79

                         90
                 ....*....|....*....
gi 357478297 518 KDYMGRVILTLTRAILEGE 536
Cdd:cd04022   80 RSFLGRVRISGTSFVPPSE 98

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 67.35 E-value: 1.66e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 442 VLSVTVISAEDLPAVDFMGKSDPFV-VLTLKKAETKNKTRVVNNSLNPVWNQTFDF--VVEDGLHDMLLV-EVYDHDTFG 517
Cdd:cd08386   17 TLTLKILKAVELPAKDFSGTSDPFVkIYLLPDKKHKLETKVKRKNLNPHWNETFLFegFPYEKLQQRVLYlQVLDYDRFS 96

                         90       100
                 ....*....|....*....|
gi 357478297 518 K-DYMGRVILTLTRAILEGE 536
Cdd:cd08386   97 RnDPIGEVSLPLNKVDLTEE 116

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. 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 here have a type-II topology.

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 67.18 E-value: 2.00e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKS--DPFVVLTL----KKAETKNKTRVV-NNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDT 515
Cdd:cd00275    4 LTIKIISGQQLPKPKGDKGSivDPYVEVEIhglpADDSAKFKTKVVkNNGFNPVWNETFEFDVTVPELAFLRFVVYDEDS 83


                 ....
gi 357478297 516 FGKD 519
Cdd:cd00275   84 GDDD 87

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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-I topology.

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 66.99 E-value: 2.41e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 440 RGVLSVTVISAEDLPAVDFMGKSDPFVVLTLKKAETKN---KTRVVNNSLNPVWNQTFDFVVEdgLHD----MLLVEVYD 512
Cdd:cd08384   12 RRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKskhKTQVKKKTLNPEFNEEFFYDIK--HSDlakkTLEITVWD 89

                         90
                 ....*....|....*....
gi 357478297 513 HDtFGK--DYMGRVILTLT 529
Cdd:cd08384   90 KD-IGKsnDYIGGLQLGIN 107

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; 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.

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 66.52 E-value: 3.35e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 442 VLSVTVISAEDLPAVDFMGKSDPFVVLT-LKKAETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGK-D 519
Cdd:cd04043    2 LFTIRIVRAENLKADSSNGLSDPYVTLVdTNGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKhD 81

                         90
                 ....*....|
gi 357478297 520 YMGRVILTLT 529
Cdd:cd04043   82 LCGRASLKLD 91

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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.

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 66.13 E-value: 3.74e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 442 VLSVTVISAEDLPAVDFMGKSDPFVVLTLKKaeTKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGKD-Y 520
Cdd:cd08376    1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLGN--EKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDeF 78

                         90
                 ....*....|
gi 357478297 521 MGRVILTLTR 530
Cdd:cd08376   79 IGRCEIDLSA 88

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 66.45 E-value: 4.40e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKT--INNDLNPIWNEHFEFIVEDASTQH--LFVKVYDDEGLQ 339
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTsvKKGTLNPVFNEAFSFDVPAEQLEEvsLVITVVDKDSVG 95

                         90
                 ....*....|....*....
gi 357478297 340 SSELIGCTDIKLSELEPGK 358
Cdd:cd00276   96 RNEVIGQVVLGPDSGGEEL 114

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (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: 176006 [Multi-domain] Cd Length: 111 Bit Score: 65.36 E-value: 5.32e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDF-MGKSDPFVVLTLKKA-ETKNKTRVVNNSLNPVWNQT-FDFVVEDGL--HDMLLVEVYDHDT 515
Cdd:cd04041    1 GVLVVTIHRATDLPKADFgTGSSDPYVTASFAKFgKPLYSTRIIRKDLNPVWEETwFVLVTPDEVkaGERLSCRLWDSDR 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 357478297 516 F-GKDYMGRVILTLtRAILEGEYKERFELDG 545
Cdd:cd04041   81 FtADDRLGRVEIDL-KELIEDRNWMGRREDG 110

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 72.10 E-value: 5.40e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTLkkAETKN-KTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGK- 518
Cdd:COG5038  1040 GYLTIMLRSGENLPSSDENGYSDPFVKLFL--NEKSVyKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKn 1117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 357478297  519 DYMGRVILTLTRAILEGEYKERFELDGAKSGFLN--LHLKW 557
Cdd:COG5038  1118 DLLGTAEIDLSKLEPGGTTNSNIPLDGKTFIVLDgtLHPGF 1158

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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.

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 65.38 E-value: 7.64e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTLKkAETKNKTRVVNNSLNPVWNQTFDFVVEDgLHDMLLVEVYDHDTFGK-DYM 521
Cdd:cd04042    2 LDIHLKEGRNLAARDRGGTSDPYVKFKYG-GKTVYKSKTIYKNLNPVWDEKFTLPIED-VTQPLYIKVFDYDRGLTdDFM 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 357478297 522 GRVILTLTRaiLEGEYKERFELD------GAKSGFLNLHLKWMP 559
Cdd:cd04042   80 GSAFVDLST--LELNKPTEVKLKledpnsDEDLGYISLVVTLTP 121

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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.

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 65.38 E-value: 8.00e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTL----KKAeTKNKTRVVNNSLNPVWNQTFDFV---VEDGLHDMLLVEVYDHDT 515
Cdd:cd04035   17 LHCTIIRAKGLKAMDANGLSDPYVKLNLlpgaSKA-TKLRTKTVHKTRNPEFNETLTYYgitEEDIQRKTLRLLVLDEDR 95

                         90
                 ....*....|....*..
gi 357478297 516 FGKDYMGRVILTLTRAI 532
Cdd:cd04035   96 FGNDFLGETRIPLKKLK 112

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. 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-II topology.

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 65.05 E-value: 9.62e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTLKKAETKNKTRVVNNSlNPVWNQTFDFVVED-GLHDM--LLVEVYDHDTF- 516
Cdd:cd04049    1 GTLEVLLISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAKGDGR-NPEWNEKFKFTVEYpGWGGDtkLILRIMDKDNFs 79

                         90       100       110
                 ....*....|....*....|....*....|.
gi 357478297 517 GKDYMGRVILTLTRAILEGEYKERFELDGAK 547
Cdd:cd04049   80 DDDFIGEATIHLKGLFEEGVEPGTAELVPAK 110

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. 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: 175999 [Multi-domain] Cd Length: 133 Bit Score: 65.07 E-value: 1.22e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 263 ILEVKLVQAKELTNKDIIGKSDPYAVLYI-RPLRNRTKKS---KTINNDLNPIWNEHFEFIVeDASTQHLFVKVYDDEGL 338
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFGASDPYVKISLyDPDGNGEIDSvqtKTIKKTLNPKWNEEFFFRV-NPREHRLLFEVFDENRL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 357478297 339 QSSELIGCTDIKLSELEPGKIKDVWLKLVKD-LEIQRDNKNRGQVHLEL 386
Cdd:cd04033   80 TRDDFLGQVEVPLNNLPTETPGNERRYTFKDyLLRPRSSKSRVKGHLRL 128

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-3 (E-Syt3) and similar proteins; Extended synaptotagmin-3 (E-Syt3), also called Chr3Syt, binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. It tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. E-Syt3 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and three C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to the SMP domain.

Pssm-ID: 439237 Cd Length: 177 Bit Score: 66.38 E-value: 1.28e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  69 QKLTWLNSHLTKIWPYVNEAASELIKTSAEPILEEyRPMILSALKFSKFTLGTVAPQFTGVSIIEDGGDG--VTMELEVQ 146
Cdd:cd21681    1 ERVEWLNKIVSQAWPYIGMIMEKKFKEKLEPKIRE-KSVHLKTFTFTKLHFGEKCPRINGVKVYTKEVDRrqVILDLQIC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 147 WDGNPSIILDIKTLvglalPVQVKNVGFTGVFRLIFKPLVNEFPGFGAVCYSLRQKKKLDFTLKVIgGDISTIPGLYDAI 226
Cdd:cd21681   80 YIGDCEINVEIKKC-----KAGVKGVQLHGTLRVILEPLLVDKPFVGAVTLFFIQKPHLEINWTGL-TNLLDIPGINDMS 153

                        170       180
                 ....*....|....*....|..
gi 357478297 227 EGAIRDAVEDSITWPVRKIVPI 248
Cdd:cd21681  154 DSLIEDLIASHLVLPNRFTVPL 175

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 64.12 E-value: 1.36e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 442 VLSVTVISAEDLPAVDFMGKSDPFVVLTLKKaeTKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTfgKDYM 521
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEPSPYVELTVGK--TTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKT--GKSL 76

                         90       100
                 ....*....|....*....|....*..
gi 357478297 522 GRVILTLTRAILEGE--YKERFELDGA 546
Cdd:cd04050   77 GSLTLPLSELLKEPDltLDQPFPLDNS 103

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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.

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 64.61 E-value: 1.45e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKK--SKTINNDLNPIWNEHFEFI---VEDASTQHLFVKVYDDEGL 338
Cdd:cd04035   17 LHCTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKlrTKTVHKTRNPEFNETLTYYgitEEDIQRKTLRLLVLDEDRF 96

                         90       100
                 ....*....|....*....|...
gi 357478297 339 qSSELIGCTDIKLSELEPGKIKD 361
Cdd:cd04035   97 -GNDFLGETRIPLKKLKPNQTKQ 118

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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-I topology.

Pssm-ID: 176012 [Multi-domain] Cd Length: 110 Bit Score: 64.12 E-value: 1.61e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 448 ISAEDLPAVDFMGKSDPFVVLTLKKAETKN----KTRVVNNSLNPVWNqTFDFVVED---GLHDM-LLVEVYDHDTFGK- 518
Cdd:cd04047    7 FSGKKLDKKDFFGKSDPFLEISRQSEDGTWvlvyRTEVIKNTLNPVWK-PFTIPLQKlcnGDYDRpIKIEVYDYDSSGKh 85

                         90       100
                 ....*....|....*....|....*
gi 357478297 519 DYMGRVILTLtRAILEGEYKErFEL 543
Cdd:cd04047   86 DLIGEFETTL-DELLKSSPLE-FEL 108

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. 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: 176070 [Multi-domain] Cd Length: 110 Bit Score: 63.87 E-value: 1.69e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVD-FMGKSDPFVVLTLkkAETKNKTRVVNNSLNPVWN-QTFDFVVEDGL--HDMLLVEVYDHDTFGK 518
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEVKF--GSTTYKTDVVKKSLNPVWNsEWFRFEVDDEElqDEPLQIRVMDHDTYSA 78

                         90
                 ....*....|..
gi 357478297 519 -DYMGRVILTLT 529
Cdd:cd08688   79 nDAIGKVYIDLN 90

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (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: 176003 [Multi-domain] Cd Length: 145 Bit Score: 64.66 E-value: 2.38e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 261 VGILEVKLVQAKELTNKDIIGkSDPYAVLYirpLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQhLFVKVYDDEGLQS 340
Cdd:cd04038    1 LGLLKVRVVRGTNLAVRDFTS-SDPYVVLT---LGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP-LKLEVFDKDTFSK 75

                         90
                 ....*....|....*.
gi 357478297 341 SELIGCTDIklsELEP 356
Cdd:cd04038   76 DDSMGEAEI---DLEP 88

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176047 [Multi-domain] Cd Length: 136 Bit Score: 63.96 E-value: 3.21e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTL---KKAETKNKTRVVNNSLNPVWNQTFDFVVEdgLHDM----LLVEVYDH 513
Cdd:cd08402   15 GKLTVVILEAKNLKKMDVGGLSDPYVKIHLmqnGKRLKKKKTTIKKRTLNPYYNESFSFEVP--FEQIqkvhLIVTVLDY 92

                         90
                 ....*....|....
gi 357478297 514 DTFGK-DYMGRVIL 526
Cdd:cd08402   93 DRIGKnDPIGKVVL 106

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. 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. The members here have topology I.

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 63.94 E-value: 3.21e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTLkkAETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFG-KD 519
Cdd:cd08375   15 GRLMVVIVEGRDLKPCNSNGKSDPYCEVSM--GSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSpDD 92


                 ....
gi 357478297 520 YMGR 523
Cdd:cd08375   93 FLGR 96

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175996 [Multi-domain] Cd Length: 127 Bit Score: 63.45 E-value: 4.16e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNR--TKKSKTINNDLNPIWNEHFEFIV--EDASTQHLFVKVYDDEGLQ 339
Cdd:cd04030   18 LIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKstRRKTSVKKDNLNPVFDETFEFPVslEELKRRTLDVAVKNSKSFL 97

                         90       100
                 ....*....|....*....|.
gi 357478297 340 SSE--LIGCTDIKLSELEPGK 358
Cdd:cd04030   98 SREkkLLGQVLIDLSDLDLSK 118

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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.

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 63.12 E-value: 4.51e-12

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKkskTINNDLNPIWNEHFEFIVEDAS---TQHLFVKVYDDE 336
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTR---TKPKDLNPVWNEKLVFNVSDPSrlsNLVLEVYVYNDR 74

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. 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-I topology.

Pssm-ID: 175991 [Multi-domain] Cd Length: 123 Bit Score: 62.89 E-value: 5.23e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVvltlkKAETKNKTR---VVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGK- 518
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFV-----RVFYNGQTLetsVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKn 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 357478297 519 DYMGRVILTLTRAILEGEYKERFEL---------DGAKSGFLNLHLK 556
Cdd:cd04025   77 DFLGKVVFSIQTLQQAKQEEGWFRLlpdpraeeeSGGNLGSLRLKVR 123

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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 fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 63.33 E-value: 5.30e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 450 AEDLPAVDFMGKSDPFV-VLTLKKAETknkTRVVNNSLNPVWNQTFDF---VVEDGLHDMLL------VEVYDHDTFGKD 519
Cdd:cd04017   10 ARDLLAADKSGLSDPFArVSFLNQSQE---TEVIKETLSPTWDQTLIFdevELYGSPEEIAQnpplvvVELFDQDSVGKD 86


                 ....*..
gi 357478297 520 -YMGRVI 525
Cdd:cd04017   87 eFLGRSV 93

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 62.61 E-value: 6.76e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDIIGKSDPYA-VLyirpLRNRTK-KSKTINNDLNPIWNEHFEFIVEdASTQHLFVKVYDDEGLQ 339
Cdd:cd04045    1 GVLRLHIRKANDLKNLEGVGKIDPYVrVL----VNGIVKgRTVTISNTLNPVWDEVLYVPVT-SPNQKITLEVMDYEKVG 75

                         90
                 ....*....|....*
gi 357478297 340 SSELIGCTDIKLSEL 354
Cdd:cd04045   76 KDRSLGSVEINVSDL 90

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-1 (E-Syt1) and similar proteins; Extended synaptotagmin-1 (E-Syt1), also called membrane-bound C2 domain-containing protein (MBC2), binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. It also binds calcium via the C2 domains and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels. E-Syt1 tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. E-Syt1 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and five C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to the SMP domain.

Pssm-ID: 439235 Cd Length: 176 Bit Score: 64.04 E-value: 7.29e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  69 QKLTWLNSHLTKIWPYVNEAASELIKTSAEPILEEYRPMiLSALKFSKFTLGTVAPQFTGVSI-IEDGGDGVTMELEVQW 147
Cdd:cd21679    1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAPAIRASNNH-LQTFSFTKVDLGEKPLKVVGVKAhTEFDKRQIILDLHISY 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 148 DGNPSIILDIKTLVGLAlpvQVKNVGFTGVFRLIFKPLVNEFPGFGAVCYSLRQKKKLDFTLKVIgGDISTIPGLYDAIE 227
Cdd:cd21679   80 VGDVEINVEVKKYFCKA---GVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGM-TNLLDIPGLSSMSD 155

                        170       180
                 ....*....|....*....|.
gi 357478297 228 GAIRDAVEDSITWPVRKIVPI 248
Cdd:cd21679  156 TMIMDTIASFLVLPNRLTVPL 176

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 62.22 E-value: 1.01e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTLKKaETKNKTRVVNNSLNPVWNQTFDFVVEDgLHDMLLVEVYDHDTFGKD 519
Cdd:cd04045    1 GVLRLHIRKANDLKNLEGVGKIDPYVRVLVNG-IVKGRTVTISNTLNPVWDEVLYVPVTS-PNQKITLEVMDYEKVGKD 77

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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.

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 62.27 E-value: 1.07e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 357478297 446 TVISAEDLPAvdFMGKSDPFVVLTLKkaETKNKTRVVNNSLNPVWNQTFDFVVEDGLH--DMLLVEVYDHDTFGKD 519
Cdd:cd08373    1 LVVSLKNLPG--LKGKGDRIAKVTFR--GVKKKTRVLENELNPVWNETFEWPLAGSPDpdESLEIVVKDYEKVGRN 72

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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.

Pssm-ID: 176013 [Multi-domain] Cd Length: 120 Bit Score: 61.82 E-value: 1.11e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 448 ISAEDLPAVDFMGKSDPFVVLTLKKAETKN-----KTRVVNNSLNPVWNQTfdFVVEDGLHDM--LLVEVYDHDTFGK-- 518
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVYVKTGGSGQwveigRTEVIKNNLNPDFVTT--FTVDYYFEEVqkLRFEVYDVDSKSKdl 84

                         90
                 ....*....|...
gi 357478297 519 ---DYMGRVILTL 528
Cdd:cd04048   85 sdhDFLGEAECTL 97

Synaptotagmin-like mitochondrial-lipid-binding domain; SMP is a proposed lipid-binding module, ie a synaptotagmin-like mitochondrial-lipid-binding domain found in eukaryotes. The SMP domain has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain. The SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell.

Pssm-ID: 465339 Cd Length: 180 Bit Score: 63.52 E-value: 1.19e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297   67 NRQKLTWLNSHLTKIWPYVNEAASELIKTSAEPILEEYRPMiLSALKFSKFTLGTVAPQFTGVSIIEDGGDG--VTMELE 144
Cdd:pfam17047   1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTH-LSTFSFTKVDVGQQPLRINGVKVYTENVDKrqIILDLQ 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  145 VQWDGNPSIILDIKTLVGLAlpvQVKNVGFTGVFRLIFKPLVNEFPGFGAVCYSLRQKKKLDFTLKVIgGDISTIPGLYD 224
Cdd:pfam17047  80 ISFVGNCEIDLEIKRYFCRA---GVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGL-TNLLDVPGLNG 155

                         170       180
                  ....*....|....*....|....*
gi 357478297  225 AIEGAIRDAVEDSITWPVRKIVPIL 249
Cdd:pfam17047 156 LSDTIILDIISNYLVLPNRITVPLV 180

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176031 [Multi-domain] Cd Length: 124 Bit Score: 61.51 E-value: 1.63e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTINNDLNPIWNEHFEFIV--EDASTQHLFVKVYDDEGLQSS 341
Cdd:cd08385   18 LTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLNPVFNETFTFKVpySELGNKTLVFSVYDFDRFSKH 97

                         90       100       110
                 ....*....|....*....|....*....|
gi 357478297 342 ELIGCTDIKLSELEPGKIKDVWlklvKDLE 371
Cdd:cd08385   98 DLIGEVRVPLLTVDLGHVTEEW----RDLE 123

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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 fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 61.41 E-value: 1.87e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 357478297 445 VTVISAEDLPAVDFMGKSDPFVVLTLKKAETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGKD 519
Cdd:cd04037    4 VYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSD 78

C2 domain second repeat in Munc13 (mammalian uncoordinated) 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.

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 61.05 E-value: 2.77e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVvlTLKKAETKNKTRVVNNSLNPVWNQTFDFVVEDGlHDMLLVEVYDHDtfgKDYMG 522
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYV--TVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNS-SDRIKVRVWDED---DDIKS 76


                 ....*...
gi 357478297 523 RVILTLTR 530
Cdd:cd04027   77 RLKQKFTR 84

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176047 [Multi-domain] Cd Length: 136 Bit Score: 60.88 E-value: 3.81e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTI--NNDLNPIWNEHFEFIVEDASTQ--HLFVKVYDDEG 337
Cdd:cd08402   15 GKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTikKRTLNPYYNESFSFEVPFEQIQkvHLIVTVLDYDR 94


                 ....*...
gi 357478297 338 LQSSELIG 345
Cdd:cd08402   95 IGKNDPIG 102

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 59.89 E-value: 3.84e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 263 ILEVKLVQAKELTNKDIIGKSDPYAVLyirPLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSse 342
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEPSPYVEL---TVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKS-- 75

                         90       100
                 ....*....|....*....|....*.
gi 357478297 343 lIGCTDIKLSEL--EPGKIKDVWLKL 366
Cdd:cd04050   76 -LGSLTLPLSELlkEPDLTLDQPFPL 100

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. 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: 176016 [Multi-domain] Cd Length: 125 Bit Score: 60.71 E-value: 4.01e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTLkKAETKNKTRVVNN-SLNPVWNQTFDFVVEDGL----HDMLLVEVYDHDTFG 517
Cdd:cd04051    2 LEITIISAEDLKNVNLFGKMKVYAVVWI-DPSHKQSTPVDRDgGTNPTWNETLRFPLDERLlqqgRLALTIEVYCERPSL 80


                 ..
gi 357478297 518 KD 519
Cdd:cd04051   81 GD 82

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 60.60 E-value: 4.30e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 258 LKPVGILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTI--NNDLNPIWNEHFEFIVEDASTQH--LFVKVY 333
Cdd:cd08403   10 LPTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRLKKKKTSvkKNTLNPTYNEALVFDVPPENVDNvsLIIAVV 89

                         90       100       110
                 ....*....|....*....|....*....|....
gi 357478297 334 DDEGLQSSELIGCtdIKLSELEPGKIKDVWLKLV 367
Cdd:cd08403   90 DYDRVGHNELIGV--CRVGPNADGQGREHWNEML 121

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 60.60 E-value: 4.43e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTL---KKAETKNKTRVVNNSLNPVWNQT--FDFVVEDGLHDMLLVEVYDHDT 515
Cdd:cd08403   14 GRLTLTIIKARNLKAMDITGFSDPYVKVSLmceGRRLKKKKTSVKKNTLNPTYNEAlvFDVPPENVDNVSLIIAVVDYDR 93


                 ..
gi 357478297 516 FG 517
Cdd:cd08403   94 VG 95

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. 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: 175999 [Multi-domain] Cd Length: 133 Bit Score: 60.44 E-value: 4.96e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 442 VLSVTVISAEDLPAVDFMGKSDPFVVLTLKKAETKN-----KTRVVNNSLNPVWNQTFDFVVEDGLHDMLLvEVYDHDTF 516
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPDGNGeidsvQTKTIKKTLNPKWNEEFFFRVNPREHRLLF-EVFDENRL 79

                         90       100
                 ....*....|....*....|....*
gi 357478297 517 GKD-YMGRVILTLTRAILEGEYKER 540
Cdd:cd04033   80 TRDdFLGQVEVPLNNLPTETPGNER 104

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 here have type-II topology.

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 59.63 E-value: 8.76e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTLKKAETKnKTRVVNNSLNPVWNQTFDFVVedGLHDMLLVEVYDHDTFGK 518
Cdd:cd08382    2 VRLTVLCADGLAKRDLFRLPDPFAVITVDGGQTH-STDVAKKTLDPKWNEHFDLTV--GPSSIITIQVFDQKKFKK 74

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. 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 synaptotagmin1. 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: 176063 [Multi-domain] Cd Length: 118 Bit Score: 59.18 E-value: 1.04e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFVVLTLkkAETKNKTRVVNNS-LNPVWNQTFDF-VVEDGLHdMLLVEVYDHDTFGK 518
Cdd:cd08681    1 GTLVVVVLKARNLPNKRKLDKQDPYCVLRI--GGVTKKTKTDFRGgQHPEWDEELRFeITEDKKP-ILKVAVFDDDKRKP 77

                         90       100
                 ....*....|....*....|....*.
gi 357478297 519 DYMGRVILTLTRAILEGEYKERFELD 544
Cdd:cd08681   78 DLIGDTEVDLSPALKEGEFDDWYELT 103

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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 here have a type-I topology.

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 58.81 E-value: 1.99e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRP-LRNRTK-KSKTINNDLNPIWNEHFEFIVEDAS-TQHLFVKVYDDEGLQS 340
Cdd:cd04026   15 LTVEVREAKNLIPMDPNGLSDPYVKLKLIPdPKNETKqKTKTIKKTLNPVWNETFTFDLKPADkDRRLSIEVWDWDRTTR 94

                         90       100
                 ....*....|....*....|....*.
gi 357478297 341 SELIGCTDIKLSELEPgKIKDVWLKL 366
Cdd:cd04026   95 NDFMGSLSFGVSELIK-MPVDGWYKL 119

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 64.01 E-value: 2.04e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  258 LKPVGILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRtkKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEG 337
Cdd:COG5038  1036 VENSGYLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVY--KTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDS 1113

                          90       100
                  ....*....|....*....|.
gi 357478297  338 LQSSELIGCTDIKLSELEPGK 358
Cdd:COG5038  1114 GEKNDLLGTAEIDLSKLEPGG 1134

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176036 [Multi-domain] Cd Length: 123 Bit Score: 57.65 E-value: 3.42e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGK-SDPYAVLYIRPLRNRTKKSKTINNDLNPIWNEHFEFIV--EDASTQHLFVKVYDDEGLQS 340
Cdd:cd08390   16 LTVSLIKARNLPPRTKDVAhCDPFVKVCLLPDERRSLQSKVKRKTQNPNFDETFVFQVsfKELQRRTLRLSVYDVDRFSR 95

                         90       100
                 ....*....|....*....|....*...
gi 357478297 341 SELIGCTDIKLSELEPGKIKDVWLKLVK 368
Cdd:cd08390   96 HCIIGHVLFPLKDLDLVKGGVVWRDLEP 123

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 57.72 E-value: 4.39e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTINNDLNPIWNE--HFE-FIVEDASTQHLFVKVYDDEGLQS 340
Cdd:cd08386   18 LTLKILKAVELPAKDFSGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNEtfLFEgFPYEKLQQRVLYLQVLDYDRFSR 97

                         90       100
                 ....*....|....*....|....*.
gi 357478297 341 SELIGCTDIKLSELEPGKIKDVWLKL 366
Cdd:cd08386   98 NDPIGEVSLPLNKVDLTEEQTFWKDL 123

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 57.59 E-value: 4.97e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFV----VLTLKKAETKnKTRVVNNSLNPVWNQTFDF-VVEDGLHDM-LLVEVYDHD 514
Cdd:cd08410   14 GRLNVDIIRAKQLLQTDMSQGSDPFVkiqlVHGLKLIKTK-KTSCMRGTIDPFYNESFSFkVPQEELENVsLVFTVYGHN 92

                         90
                 ....*....|...
gi 357478297 515 TFGK-DYMGRVIL 526
Cdd:cd08410   93 VKSSnDFIGRIVI 105

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 57.44 E-value: 5.49e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTLKKAE---TKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVE--VYDHDTFG 517
Cdd:cd08404   17 LTVVVLKARHLPKMDVSGLADPYVKVNLYYGKkriSKKKTHVKKCTLNPVFNESFVFDIPSEELEDISVEflVLDSDRVT 96

                         90
                 ....*....|
gi 357478297 518 K-DYMGRVIL 526
Cdd:cd08404   97 KnEVIGRLVL 106

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; 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.

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 57.27 E-value: 5.60e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 266 VKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSELIG 345
Cdd:cd04043    5 IRIVRAENLKADSSNGLSDPYVTLVDTNGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHDLCG 84

                         90       100
                 ....*....|....*....|....*..
gi 357478297 346 CTDIKLSelePGKIKD------VWLKL 366
Cdd:cd04043   85 RASLKLD---PKRFGDdglpreIWLDL 108

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. 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: 176016 [Multi-domain] Cd Length: 125 Bit Score: 56.86 E-value: 7.41e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 263 ILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRnrtKKSKTINND--LNPIWNEHFEFIVEDASTQH----LFVKVYDDE 336
Cdd:cd04051    1 TLEITIISAEDLKNVNLFGKMKVYAVVWIDPSH---KQSTPVDRDggTNPTWNETLRFPLDERLLQQgrlaLTIEVYCER 77

                         90
                 ....*....|....*...
gi 357478297 337 GLQSSELIGCTDIKLSEL 354
Cdd:cd04051   78 PSLGDKLIGEVRVPLKDL 95

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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.

Pssm-ID: 176013 [Multi-domain] Cd Length: 120 Bit Score: 56.81 E-value: 7.79e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 269 VQAKELTNKDIIGKSDPYAVLYIRPLRNR--TKKSKT--INNDLNPIWNE--HFEFIVEdaSTQHLFVKVYDDEG----L 338
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVYVKTGGSGqwVEIGRTevIKNNLNPDFVTtfTVDYYFE--EVQKLRFEVYDVDSkskdL 84

                         90
                 ....*....|....*.
gi 357478297 339 QSSELIGCTDIKLSEL 354
Cdd:cd04048   85 SDHDFLGEAECTLGEI 100

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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.

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 56.49 E-value: 1.01e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 269 VQAKELTNKdiIGKSDPYAVLYIRPLrnrTKKSKTINNDLNPIWNEHFEFIVE---DASTQhLFVKVYDDEGLQSSELIG 345
Cdd:cd08373    3 VSLKNLPGL--KGKGDRIAKVTFRGV---KKKTRVLENELNPVWNETFEWPLAgspDPDES-LEIVVKDYEKVGRNRLIG 76


                 ....*....
gi 357478297 346 CTDIKLSEL 354
Cdd:cd08373   77 SATVSLQDL 85

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 56.66 E-value: 1.02e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTI--NNDLNPIWNEHFEFIV--EDASTQHLFVKVYDDEG 337
Cdd:cd08405   15 NRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVEKKKTVikKRTLNPVFNESFIFNIplERLRETTLIITVMDKDR 94


                 ....*...
gi 357478297 338 LQSSELIG 345
Cdd:cd08405   95 LSRNDLIG 102

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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.

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 55.72 E-value: 1.96e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGK-SDPFV---VLTLKKAETKNKTRVVNNSLNPVWNQTFDFVVEdglHDMLL-----VEVY 511
Cdd:cd08521   14 GSLEVHIKECRNLAYADEKKKrSNPYVkvyLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHIS---KSQLEtrtlqLSVW 90

                         90
                 ....*....|....*....
gi 357478297 512 DHDTFG-KDYMGRVILTLT 529
Cdd:cd08521   91 HHDRFGrNTFLGEVEIPLD 109

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176034 [Multi-domain] Cd Length: 128 Bit Score: 55.05 E-value: 3.75e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 440 RGVLSVTVISAEDLPAVDF-MGKSDPFVVLT-LKKAETKNKTRVVNNSLNPVWNQTFDF--VVEDGLHDMLL-VEVYDHD 514
Cdd:cd08388   15 KKALLVNIIECRDLPAMDEqSGTSDPYVKLQlLPEKEHKVKTRVLRKTRNPVYDETFTFygIPYNQLQDLSLhFAVLSFD 94

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 357478297 515 TFGKD-YMGRVILTLTrailegeykerfELDGAKSGFLNLHLKWMP 559
Cdd:cd08388   95 RYSRDdVIGEVVCPLA------------GADLLNEGELLVSREIQP 128

C2 domain second repeat in Munc13 (mammalian uncoordinated) 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.

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 54.88 E-value: 3.90e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKkskTINNDLNPIWNEHFEFIVEDaSTQHLFVKVYDDEG------ 337
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTK---TIPQNLNPVWNEKFHFECHN-SSDRIKVRVWDEDDdiksrl 78

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 357478297 338 -----LQSSELIGCTDIKLSELEpGKIkDVWLKLVK 368
Cdd:cd04027   79 kqkftRESDDFLGQTIIEVRTLS-GEM-DVWYNLEK 112

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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 fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 54.48 E-value: 4.38e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 266 VKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKsKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSELIG 345
Cdd:cd04037    4 VYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRD-NYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDLIG 82


                 ....*.
gi 357478297 346 CTDIKL 351
Cdd:cd04037   83 ETVIDL 88

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. 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 here have a type-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 54.30 E-value: 7.76e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKdIIGKSDPYA-VLYIRPLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSE 342
Cdd:cd08675    1 LSVRVLECRDLALK-SNGTCDPFArVTLNYSSKTDTKRTKVKKKTNNPRFDEAFYFELTIGFSYEKKSFKVEEEDLEKSE 79


                 ..
gi 357478297 343 LI 344
Cdd:cd08675   80 LR 81

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. 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-I topology.

Pssm-ID: 175991 [Multi-domain] Cd Length: 123 Bit Score: 53.64 E-value: 9.02e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYA-VLYirplRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSE 342
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFVrVFY----NGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKND 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 357478297 343 LIGCTDIKLSELEPGKIKDVWLKLVKDLEIQRDNK-NRGQVHLEL 386
Cdd:cd04025   78 FLGKVVFSIQTLQQAKQEEGWFRLLPDPRAEEESGgNLGSLRLKV 122

C2 domain second 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175976 [Multi-domain] Cd Length: 133 Bit Score: 53.78 E-value: 1.02e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRP----LRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQH-----LFVkVYD 334
Cdd:cd04009   18 LRVEILNARNLLPLDSNGSSDPFVKVELLPrhlfPDVPTPKTQVKKKTLFPLFDESFEFNVPPEQCSVegallLFT-VKD 96

                         90       100
                 ....*....|....*....|...
gi 357478297 335 DEGLQSSELIGCTDIKLSELePG 357
Cdd:cd04009   97 YDLLGSNDFEGEAFLPLNDI-PG 118

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. 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: 176004 [Multi-domain] Cd Length: 108 Bit Score: 53.03 E-value: 1.21e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKS----DPFVVLTLKKAETKnkTRVVNNSLNPVWNQTFDFVVedGLHDM---LLVEVYDH 513
Cdd:cd04039    1 GVVFMEIKSITDLPPLKNMTRTgfdmDPFVIISFGRRVFR--TSWRRHTLNPVFNERLAFEV--YPHEKnfdIQFKVLDK 76

                         90
                 ....*....|....*..
gi 357478297 514 DTF-GKDYMGRVILTLT 529
Cdd:cd04039   77 DKFsFNDYVATGSLSVQ 93

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. 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: 176011 [Multi-domain] Cd Length: 126 Bit Score: 53.44 E-value: 1.22e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 442 VLSVTVISAEDLPAVDFMGKSDPFVVLtlkKAETKN-KTRVVNNSLNPVWNQTFDFVVEDgLHDMLLVEVYDHDTFGKDY 520
Cdd:cd04046    4 VTQVHVHSAEGLSKQDSGGGADPYVII---KCEGESvRSPVQKDTLSPEFDTQAIFYRKK-PRSPIKIQVWNSNLLCDEF 79


                 ....*..
gi 357478297 521 MGRVILT 527
Cdd:cd04046   80 LGQATLS 86

C2 domain second 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. 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176027 [Multi-domain] Cd Length: 122 Bit Score: 52.68 E-value: 2.02e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 284 DPYAVLYIRP-LRNRTK-KSKTINNDLNPIWNEHF---EFIVEDASTQHLFVKVYDDEGLQSSELIGCTDIKLSELEPGK 358
Cdd:cd08381   34 DPYVKTYLLPdPQKTTKrKTKVVRKTRNPTFNEMLvydGLPVEDLQQRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQ 113


                 ....*...
gi 357478297 359 IKDVWLKL 366
Cdd:cd08381  114 ETEKWYPL 121

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. 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.

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 52.52 E-value: 2.33e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRplRNRTKKSKTINNDLNPIWNEhfEFIVEDASTQH-LFVKVYDDEGLQSSE 342
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYCIVKVD--NEVIIRTATVWKTLNPFWGE--EYTVHLPPGFHtVSFYVLDEDTLSRDD 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 357478297 343 LIGCTDIKLSEL--EPGKIkDVWLKLVkdlEIQRDNKNRGQVHLEL 386
Cdd:cd04054   78 VIGKVSLTREVIsaHPRGI-DGWMNLT---EVDPDEEVQGEIHLEL 119

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in testis-expressed protein 2 (TEX2) and similar proteins; testis-expressed protein 2 (TEX2), also called transmembrane protein 96 (TMEM96), is a transmembrane protein with uncharacterized biological function. Diseases associated with TEX2 include Wernicke-Korsakoff Syndrome. This model corresponds to the SMP domain of TEX2, which may be implicated in lipid transport.

Pssm-ID: 439231 Cd Length: 186 Bit Score: 54.04 E-value: 2.34e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 105 RPMILSALKFSKFTLGTVAPQFTGVSIIE-DGGDGVTMELEVQWDGNPSIILDIKTLVGLALPVQVKNV---------GF 174
Cdd:cd21675   36 LPSFLGEITVTDLDLGTSVPVISNPKLPSlDPDGGLWVDLDVSYRGGFSLTLETKLNLSKLKKEKVSNVplvlavevkSL 115

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 357478297 175 TGVFRLIFKPlvnefPGFGAVCYSLRQKKKLDFTLK-VIGGDISTIPGLYDAIEGAIRDAVEDSITWPVRKIVPI 248
Cdd:cd21675  116 SGTLRLNIKP-----PPSNRLWYGFREMPKLELEIEpVVGERQVTLPHVTNWIEKKLKEEIKESLVLPNMDDFPF 185

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. 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. The members here have topology I.

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 52.39 E-value: 3.88e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 261 VGILEVKLVQAKELTNKDIIGKSDPYAVLyirPLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQS 340
Cdd:cd08375   14 IGRLMVVIVEGRDLKPCNSNGKSDPYCEV---SMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSP 90

                         90
                 ....*....|....
gi 357478297 341 SELIGCTDIKLSEL 354
Cdd:cd08375   91 DDFLGRTEIRVADI 104

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. 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 here have a type-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 51.99 E-value: 4.85e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDfMGKSDPFVVLTL---KKAETKnKTRVVNNSLNPVWNQTFDFVV---------------EDGLHD 504
Cdd:cd08675    1 LSVRVLECRDLALKS-NGTCDPFARVTLnysSKTDTK-RTKVKKKTNNPRFDEAFYFELtigfsyekksfkveeEDLEKS 78

                         90       100
                 ....*....|....*....|....*
gi 357478297 505 MLLVEVYDHDT-FGKDYMGRVILTL 528
Cdd:cd08675   79 ELRVELWHASMvSGDDFLGEVRIPL 103

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. 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 here have a type-II topology.

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 51.77 E-value: 5.26e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 281 GKSDPYAVLYIR---PLRNRTKKSKTI-NNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLqSSELIGCTDIKLSELEP 356
Cdd:cd00275   23 SIVDPYVEVEIHglpADDSAKFKTKVVkNNGFNPVWNETFEFDVTVPELAFLRFVVYDEDSG-DDDFLGQACLPLDSLRQ 101


                 .
gi 357478297 357 G 357
Cdd:cd00275  102 G 102

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 52.29 E-value: 5.38e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTLKKaeTKNKTRV-VNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGKD-Y 520
Cdd:cd04019    2 LRVTVIEAQDLVPSDKNRVPEVFVKAQLGN--QVLRTRPsQTRNGNPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDeP 79


                 ....*....
gi 357478297 521 MGRVILTLT 529
Cdd:cd04019   80 LGRAVIPLN 88

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). 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 here have a type-I topology and do not bind Ca2+.

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 51.09 E-value: 6.80e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKK--SKTINNDLNPIWNEHFEFIV---EDASTQHLFVKVYDDE 336
Cdd:cd04031   16 SQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKrrTKTVKKTLNPEWNQTFEYSNvrrETLKERTLEVTVWDYD 95

                         90
                 ....*....|....*.
gi 357478297 337 GLQSSELIGCTDIKLS 352
Cdd:cd04031   96 RDGENDFLGEVVIDLA 111

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. 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: 175998 [Multi-domain] Cd Length: 127 Bit Score: 51.49 E-value: 6.91e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 440 RGVLSVTVISAEDLPAvDFMGKSDPFVVLTLKKAEtkNKTRVVNNSLNPVWNQTFDF-VVEDGLHDMLLVEVYDHDTFGK 518
Cdd:cd04032   27 LATLTVTVLRATGLWG-DYFTSTDGYVKVFFGGQE--KRTEVIWNNNNPRWNATFDFgSVELSPGGKLRFEVWDRDNGWD 103


                 .
gi 357478297 519 D 519
Cdd:cd04032  104 D 104

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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.

Pssm-ID: 176024 [Multi-domain] Cd Length: 121 Bit Score: 50.77 E-value: 8.10e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAvdfmGKSDPFVVLTLkkAETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGKDYMG 522
Cdd:cd08378    2 LYVRVVKARGLPA----NSNDPVVEVKL--GNYKGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWDKDKAKDDFLG 75


                 ..
gi 357478297 523 RV 524
Cdd:cd08378   76 GV 77

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 50.86 E-value: 8.46e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 441 GVLSVTVISAEDLPAVDFMGKSDPFV-VLTLKKAETKNKTRVVNNSLNPVWNQTFDF-VVEDGLHDMLL-VEVYDHDTFG 517
Cdd:cd08387   16 GILNVKLIQARNLQPRDFSGTADPYCkVRLLPDRSNTKQSKIHKKTLNPEFDESFVFeVPPQELPKRTLeVLLYDFDQFS 95

                         90
                 ....*....|..
gi 357478297 518 KD-YMGRVILTL 528
Cdd:cd08387   96 RDeCIGVVELPL 107

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. 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: 175988 [Multi-domain] Cd Length: 125 Bit Score: 51.12 E-value: 8.82e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKeLTNKDIIGKSDPYAVLYIRPLRnrTKKSKTINNDLNPIWNEHFEFIVEDASTQHLfvKVYDDEGLQSSEL 343
Cdd:cd04021    4 LQITVESAK-LKSNSKSFKPDPYVEVTVDGQP--PKKTEVSKKTSNPKWNEHFTVLVTPQSTLEF--KVWSHHTLKADVL 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 357478297 344 IGCTDIKLSEL---EPGKIKDVwlKLVkdLEIQRDNKNR 379
Cdd:cd04021   79 LGEASLDLSDIlknHNGKLENV--KLT--LNLSSENKGS 113

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176036 [Multi-domain] Cd Length: 123 Bit Score: 49.95 E-value: 1.73e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 438 IIRGVLSVTVISAEDLPAVDF-MGKSDPFVVLTL-------KKAETKNKTrvvnnsLNPVWNQTFDFVV--EDGLHDMLL 507
Cdd:cd08390   11 LEEEQLTVSLIKARNLPPRTKdVAHCDPFVKVCLlpderrsLQSKVKRKT------QNPNFDETFVFQVsfKELQRRTLR 84

                         90       100
                 ....*....|....*....|..
gi 357478297 508 VEVYDHDTFGKDY-MGRVILTL 528
Cdd:cd08390   85 LSVYDVDRFSRHCiIGHVLFPL 106

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. 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: 175982 [Multi-domain] Cd Length: 158 Bit Score: 50.77 E-value: 1.79e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 435 KEVIIRGVLSVTVISAEDLPAVDFMGK------------------------------SDPFVVLTLKKAeTKNKTRVVNN 484
Cdd:cd04015    1 AAVLLHGTLDVTIYEADNLPNMDMFSEklrrffsklvgcseptlkrpsshrhvgkitSDPYATVDLAGA-RVARTRVIEN 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 357478297 485 SLNPVWNQTFDFVVEdglHDMLLVE--VYDHDTFGKDYMGRVILTLtRAILEGEYKERF 541
Cdd:cd04015   80 SENPVWNESFHIYCA---HYASHVEftVKDNDVVGAQLIGRAYIPV-EDLLSGEPVEGW 134

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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.

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 49.52 E-value: 1.80e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 272 KEL-TNKDIIGKSDPYAVLYIRplRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDeGLQSSELIGCTDIK 350
Cdd:cd04052    1 KGLdTSESKTGLLSPYAELYLN--GKLVYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDD-RDRHDPVLGSVSIS 77


                 ....
gi 357478297 351 LSEL 354
Cdd:cd04052   78 LNDL 81

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 49.89 E-value: 2.63e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 258 LKPVGILEVKLVQAKELTNKDIIGKSDPYA-VLYIRPLR-NRTKKSKTINNDLNPIWNEHFEFIV--EDASTQHLFVKVY 333
Cdd:cd08410   10 LPSAGRLNVDIIRAKQLLQTDMSQGSDPFVkIQLVHGLKlIKTKKTSCMRGTIDPFYNESFSFKVpqEELENVSLVFTVY 89

                         90
                 ....*....|..
gi 357478297 334 DDEGLQSSELIG 345
Cdd:cd08410   90 GHNVKSSNDFIG 101

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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-I topology.

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 49.65 E-value: 2.67e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKTI--NNDLNPIWNEHFEFIV--EDASTQHLFVKVYD-DE 336
Cdd:cd08384   13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQvkKKTLNPEFNEEFFYDIkhSDLAKKTLEITVWDkDI 92


                 ....*....
gi 357478297 337 GlQSSELIG 345
Cdd:cd08384   93 G-KSNDYIG 100

cellulose synthase-interactive protein; Provisional

Pssm-ID: 215629 [Multi-domain] Cd Length: 2102 Bit Score: 53.18 E-value: 4.51e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297  441 GVLSVTVISAEDLPAVdfMGKSDPFVVLTLKKAETKnKTRVVNNSLNPVWNQTFDFVVE-----DGLHdmllVEVYDHDT 515
Cdd:PLN03200 1980 GSLTVTIKRGNNLKQS--MGNTNAFCKLTLGNGPPR-QTKVVSHSSSPEWKEGFTWAFDsppkgQKLH----ISCKSKNT 2052

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 357478297  516 FGKDYMGRVILTLTRAILEGEYKERFEL--DGAKSG 549
Cdd:PLN03200 2053 FGKSSLGKVTIQIDRVVMEGTYSGEYSLnpESNKDG 2088

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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-I topology.

Pssm-ID: 176012 [Multi-domain] Cd Length: 110 Bit Score: 48.33 E-value: 5.30e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 271 AKELTNKDIIGKSDPYAVLYiRPLRNRTK----KSKTINNDLNPIWNehfEFIVE-------DAStQHLFVKVYDDEGLQ 339
Cdd:cd04047    9 GKKLDKKDFFGKSDPFLEIS-RQSEDGTWvlvyRTEVIKNTLNPVWK---PFTIPlqklcngDYD-RPIKIEVYDYDSSG 83

                         90       100
                 ....*....|....*....|..
gi 357478297 340 SSELIGCTDIKLSELEPGKIKD 361
Cdd:cd04047   84 KHDLIGEFETTLDELLKSSPLE 105

C2 domain second 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. 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176027 [Multi-domain] Cd Length: 122 Bit Score: 48.44 E-value: 5.94e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 440 RGVLSVTVISAEDLPAVDfmGKS-DPFVVLTLK---KAETKNKTRVVNNSLNPVWNQTfdfVVEDGLHDMLL------VE 509
Cdd:cd08381   12 NGTLFVMVMHAKNLPLLD--GSDpDPYVKTYLLpdpQKTTKRKTKVVRKTRNPTFNEM---LVYDGLPVEDLqqrvlqVS 86

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 357478297 510 VYDHDTFG-KDYMGRVILTLTRAILEGEYKERFEL 543
Cdd:cd08381   87 VWSHDSLVeNEFLGGVCIPLKKLDLSQETEKWYPL 121

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 48.58 E-value: 5.98e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDF-MGKSDPFV---VLTLKKAETKNKTRVVNNSLNPVWNQTFDFVVE--DGLHDMLLVEVYDHDTF 516
Cdd:cd08393   17 LHVHVIQCQDLAAADPkKQRSDPYVktyLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEreELPTRVLNLSVWHRDSL 96

                         90
                 ....*....|...
gi 357478297 517 GKD-YMGRVILTL 528
Cdd:cd08393   97 GRNsFLGEVEVDL 109

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. 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: 175988 [Multi-domain] Cd Length: 125 Bit Score: 47.66 E-value: 1.12e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 357478297 443 LSVTVISAEdLPAVDFMGKSDPFVVLTLKKAETKnKTRVVNNSLNPVWNQTFDFVVEDglHDMLLVEVYDHDTFGKDYM 521
Cdd:cd04021    4 LQITVESAK-LKSNSKSFKPDPYVEVTVDGQPPK-KTEVSKKTSNPKWNEHFTVLVTP--QSTLEFKVWSHHTLKADVL 78

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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 fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 47.92 E-value: 1.26e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYA-VLYirplRNRTKKSKTINNDLNPIWNEH--FEFIVEDASTQHL-------FVKVY 333
Cdd:cd04017    3 LRAYIYQARDLLAADKSGLSDPFArVSF----LNQSQETEVIKETLSPTWDQTliFDEVELYGSPEEIaqnpplvVVELF 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 357478297 334 DDEGLQSSELIGCTDIK------LSELEPGKIKdvWLKlvkdleIQRDNKNRGQV 382
Cdd:cd04017   79 DQDSVGKDEFLGRSVAKplvkldLEEDFPPKLQ--WFP------IYKGGQSAGEL 125

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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-I topology.

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 48.09 E-value: 2.05e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 248 ILPGDYSDLELKPV--GILEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKT--INNDLNPIWNEHFEF---IV 320
Cdd:cd04020   11 VPPESEGALKSKKPstGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTpvVKKSVNPVWNHTFVYdgvSP 90

                         90       100
                 ....*....|....*....|....*..
gi 357478297 321 EDASTQHLFVKVYDDEGLQSSELIGCT 347
Cdd:cd04020   91 EDLSQACLELTVWDHDKLSSNDFLGGV 117

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. 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: 176060 [Multi-domain] Cd Length: 126 Bit Score: 46.98 E-value: 2.57e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVdfMGKSDPFVVLTLKKAETKNKTRVVNNSLNPVWNQTFDFVVeDGLHDMLLVEVYDH--------- 513
Cdd:cd08678    1 LLVKNIKANGLSEA--AGSSNPYCVLEMDEPPQKYQSSTQKNTSNPFWDEHFLFEL-SPNSKELLFEVYDNgkksdskfl 77

                         90       100       110
                 ....*....|....*....|....*....|
gi 357478297 514 -------DTFGKDYMGRVILTLTRAILEGE 536
Cdd:cd08678   78 glaivpfDELRKNPSGRQIFPLQGRPYEGD 107

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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.

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 46.48 E-value: 3.16e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKELTNKDIIGK-SDPYAVLYIRPLRNRTKKSKTI--NNDLNPIWNEHFEFIVE--DASTQHLFVKVYDDE 336
Cdd:cd08521   14 GSLEVHIKECRNLAYADEKKKrSNPYVKVYLLPDKSKQSKRKTSvkKNTTNPVFNETLKYHISksQLETRTLQLSVWHHD 93

                         90       100       110
                 ....*....|....*....|....*....|
gi 357478297 337 GLQSSELIGCTDIKLSELEPGKIKDVWLKL 366
Cdd:cd08521   94 RFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 46.89 E-value: 3.37e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 297 RTKKSKTINNdlNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSELIGCTDIKLSELE----PGKIKDVWLKLVKDLEI 372
Cdd:cd04019   35 RTRPSQTRNG--NPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDEPLGRAVIPLNDIErrvdDRPVPSRWFSLERPGGA 112

                         90
                 ....*....|....*..
gi 357478297 373 QRDNKNR---GQVHLEL 386
Cdd:cd04019  113 MEQKKKRkfaSRIHLRL 129

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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-I topology.

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 46.65 E-value: 3.52e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPLRNRTKKSKT--INNDLNPIWNEHFEFIVEDASTQHLFVK--VYDDEGLQ 339
Cdd:cd08404   17 LTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKThvKKCTLNPVFNESFVFDIPSEELEDISVEflVLDSDRVT 96


                 ....*.
gi 357478297 340 SSELIG 345
Cdd:cd08404   97 KNEVIG 102

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 here have type-II topology.

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 45.38 E-value: 6.55e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 357478297 264 LEVKLVQAKELTNKDIIGKSDPYAVLYIRPlrNRTKKSKTINNDLNPIWNEHFEFIVEDASTqhLFVKVYD 334
Cdd:cd08382    2 VRLTVLCADGLAKRDLFRLPDPFAVITVDG--GQTHSTDVAKKTLDPKWNEHFDLTVGPSSI--ITIQVFD 68

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. 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 here have a type-I topology.

Pssm-ID: 176029 [Multi-domain] Cd Length: 117 Bit Score: 45.33 E-value: 6.68e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKdiiGKSDPYAVLYIrplrNRTKKSKT-INNDLNPIWNEhfEFIVED----ASTQHLFVKVYDDEGL 338
Cdd:cd08383    2 LRLRILEAKNLPSK---GTRDPYCTVSL----DQVEVARTkTVEKLNPFWGE--EFVFDDpppdVTFFTLSFYNKDKRSK 72

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 357478297 339 QSSELIGctDIKLSELEPGKIKDVWLKL---VKDLEIQrdnknrGQVHLELLY 388
Cdd:cd08383   73 DRDIVIG--KVALSKLDLGQGKDEWFPLtpvDPDSEVQ------GSVRLRARY 117

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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.

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 45.51 E-value: 7.06e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 461 KSDPFV---VLTLKKAETKNKTRVVNNSLNPVWNQTFDFVV-EDGLHD-MLLVEVYDHDTFGKD-YMGRVILTLTRAILE 534
Cdd:cd04029   36 RSNPYVktyLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSIsHSQLETrTLQLSVWHYDRFGRNtFLGEVEIPLDSWNFD 115


                 ....*....
gi 357478297 535 GEYKERFEL 543
Cdd:cd04029  116 SQHEECLPL 124

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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.

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 44.90 E-value: 8.58e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 460 GKSDPFVVLTLKKAETKnKTRVVNNSLNPVWNQTFDFVVEDGLHDMLLVEVYDHDTFGKDYMGRVILTLTRAILEGEYKE 539
Cdd:cd04052   11 GLLSPYAELYLNGKLVY-TTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDDRDRHDPVLGSVSISLNDLIDATSVGQ 89

                         90       100
                 ....*....|....*....|.
gi 357478297 540 R-FELDGAKSGFLNLHLKWMP 559
Cdd:cd04052   90 QwFPLSGNGQGRIRISALWKP 110

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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.

Pssm-ID: 176035 [Multi-domain] Cd Length: 124 Bit Score: 45.31 E-value: 9.00e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDfMGKSDPF----VVLTLKKAETKNKTRVVNnslNPVWNQTFDF--VVEDGLHDM-LLVEVYDHDT 515
Cdd:cd08389   18 LTVTVIRAQDIPTKD-RGGASSWqvhlVLLPSKKQRAKTKVQRGP---NPVFNETFTFsrVEPEELNNMaLRFRLYGVER 93

                         90       100
                 ....*....|....*....|..
gi 357478297 516 FGKDYM-GRVILTLTRAILEGE 536
Cdd:cd08389   94 MRKERLiGEKVVPLSQLNLEGE 115

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. 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.

Pssm-ID: 176046 [Multi-domain] Cd Length: 121 Bit Score: 45.12 E-value: 1.04e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 300 KSKTINNDLNPIWNEHFEFIVEdASTQHLFVKVYDDEGLQSSELIGCTDIKLSELEPGKIKDVWLKLvkdLEIQRDNKNR 379
Cdd:cd08401   37 RTKTVEKSLCPFFGEDFYFEIP-RTFRHLSFYIYDRDVLRRDSVIGKVAIKKEDLHKYYGKDTWFPL---QPVDADSEVQ 112


                 ....*..
gi 357478297 380 GQVHLEL 386
Cdd:cd08401  113 GKVHLEL 119

C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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 fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 176025 [Multi-domain] Cd Length: 126 Bit Score: 45.09 E-value: 1.08e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 261 VGILEVKLVQAKELtnKDIIGKSDPYAVLYIRPLRNRTKkskTINNDLNPIWNEHFEFIVEDASTQhLFVKVYD------ 334
Cdd:cd08379    4 VGILGAQGLDVLRA--KDGRGSTDAYCVAKYGPKWVRTR---TVEDSSNPRWNEQYTWPVYDPCTV-LTVGVFDnsqshw 77

                         90       100
                 ....*....|....*....|....*
gi 357478297 335 DEGLQSSELIGCTDIKLSELEPGKI 359
Cdd:cd08379   78 KEAVQPDVLIGKVRIRLSTLEDDRV 102

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. 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.

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 44.43 E-value: 1.70e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVDFMGKSDPFVVLTLKKaETKNKTRVVNNSLNPVWNQTFDFVVEDGLHdMLLVEVYDHDTFGK-DYM 521
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYCIVKVDN-EVIIRTATVWKTLNPFWGEEYTVHLPPGFH-TVSFYVLDEDTLSRdDVI 79


                 ....*.
gi 357478297 522 GRVILT 527
Cdd:cd04054   80 GKVSLT 85

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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.

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 42.56 E-value: 5.47e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 444 SVTVISAEDLPAVDfmgkSDPFVVLTLkkAETKNKTRVVNNSLNPVWNQTFDFVVEDGLHDM----LLVEVYDHDTFGKD 519
Cdd:cd04011    7 RVRVIEARQLVGGN----IDPVVKVEV--GGQKKYTSVKKGTNCPFYNEYFFFNFHESPDELfdkiIKISVYDSRSLRSD 80

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. 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-I topology.

Pssm-ID: 175977 [Multi-domain] Cd Length: 148 Bit Score: 41.61 E-value: 2.48e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDiiGKSDPYAVLYIR--PLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSS 341
Cdd:cd04010    2 LSVRVIECSDLALKN--GTCDPYASVTLIysNKKQDTKRTKVKKKTNNPQFDEAFYFDVTIDSSPEKKQFEMPEEDAEKL 79


                 ...
gi 357478297 342 ELI 344
Cdd:cd04010   80 ELR 82

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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.

Pssm-ID: 176024 [Multi-domain] Cd Length: 121 Bit Score: 40.76 E-value: 3.29e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNkdiiGKSDPYAVLYIRPLRNRTKKsktINNDLNPIWNEHFEFIVE--DASTQHLFVKvydDEGLQSS 341
Cdd:cd08378    2 LYVRVVKARGLPA----NSNDPVVEVKLGNYKGSTKA---IERTSNPEWNQVFAFSKDrlQGSTLEVSVW---DKDKAKD 71

                         90
                 ....*....|..
gi 357478297 342 ELIGCTDIKLSE 353
Cdd:cd08378   72 DFLGGVCFDLSE 83

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 41.08 E-value: 3.76e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 443 LSVTVISAEDLPAVD--FMGK------------SDPFVVLTLkkAETKNKTRVVNNSLNPVWNQTFDFVvedglhDM--- 505
Cdd:cd04018    2 FIFKIYRAEDLPQMDsgIMANvkkaflgekkelVDPYVEVSF--AGQKVKTSVKKNSYNPEWNEQIVFP------EMfpp 73

                         90
                 ....*....|....*...
gi 357478297 506 ----LLVEVYDHDTFGKD 519
Cdd:cd04018   74 lcerIKIQIRDWDRVGND 91

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. 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: 176064 [Multi-domain] Cd Length: 126 Bit Score: 40.51 E-value: 3.83e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 444 SVTVISAEDLPAVDFMGKSDPFVVLTLKKaeTKNKTRVVNNSLNPVWNQTFDF-----VVEDGLHDMLLVEVYDHDTFGK 518
Cdd:cd08682    2 QVTVLQARGLLCKGKSGTNDAYVIIQLGK--EKYSTSVKEKTTSPVWKEECSFelpglLSGNGNRATLQLTVMHRNLLGL 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 357478297 519 D-YMGRVILTLtRAILEGEYKER---FELDGAKSG 549
Cdd:cd08682   80 DkFLGQVSIPL-NDLDEDKGRRRtrwFKLESKPGK 113

C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 receptor (IL-1R) signaling pathway. Tollip is proposed to link serine/threonine kinase IRAK to IL-1Rs as well as inhibiting phosphorylation of IRAK. There is a single C2 domain present in Tollip. 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: 175983 [Multi-domain] Cd Length: 121 Bit Score: 40.01 E-value: 4.97e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 440 RGVLSVTVISAEdLPAVDFMGKSDPFVVLTLKKAETKNKTrVVNNSLNPVWNQTFDFVVEDGLhDMLLVEVYDHDTFGKD 519
Cdd:cd04016    1 VGRLSITVVQAK-LVKNYGLTRMDPYCRIRVGHAVYETPT-AYNGAKNPRWNKTIQCTLPEGV-DSIYIEIFDERAFTMD 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 357478297 520 ymGRV---ILTLTRAILEGEYKER-FELDGA----KSGFLNLHL 555
Cdd:cd04016   78 --ERIawtHITIPESVFNGETLDDwYSLSGKqgedKEGMINLVF 119

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. 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-I topology.

Pssm-ID: 175977 [Multi-domain] Cd Length: 148 Bit Score: 40.46 E-value: 5.57e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 357478297 443 LSVTVISAEDLPAVDfmGKSDPFVVLTL----KKAETKnKTRVVNNSLNPVWNQTFDFVVE 499
Cdd:cd04010    2 LSVRVIECSDLALKN--GTCDPYASVTLiysnKKQDTK-RTKVKKKTNNPQFDEAFYFDVT 59

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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 here have a type-II topology.

Pssm-ID: 175981 [Multi-domain] Cd Length: 132 Bit Score: 39.56 E-value: 8.12e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 262 GILEVKLVQAKEL-------------TNKDIIgksDPYAVLYIRPLR-NRT-KKSKTinndLNPIWNEHFEFIVEDAstQ 326
Cdd:cd04014    4 GTLKIKICEAVDLkptdwstrhavpkKGSQLL---DPYVSIDVDDTHiGKTsTKPKT----NSPVWNEEFTTEVHNG--R 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 327 HLFVKVYDDEGLQSSELIGCTDIKLSEL--EPGKIKDVWLklvkDLEIQrdnknrGQVHL 384
Cdd:cd04014   75 NLELTVFHDAAIGPDDFVANCTISFEDLiqRGSGSFDLWV----DLEPQ------GKLHV 124

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 41.52 E-value: 1.54e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 275 TNKDIIGKSDPYAVLYI--RPLRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQHLFVKVYDDEGLQSSELIGCTDIKLS 352
Cdd:PLN02952 489 THFDSYSPPDFYTKMYIvgVPADNAKKKTKIIEDNWYPAWNEEFSFPLTVPELALLRIEVREYDMSEKDDFGGQTCLPVS 568

                         90
                 ....*....|..
gi 357478297 353 ELEPGkIKDVWL 364
Cdd:PLN02952 569 ELRPG-IRSVPL 579

Phospholipase D delta

Pssm-ID: 178585 [Multi-domain] Cd Length: 868 Bit Score: 41.23 E-value: 1.84e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 357478297 462 SDPFVVLTLKKAeTKNKTRVVNNSLNPVWNQTFDFVVEDGLHdMLLVEVYDHDTFGKDYMGRVILTLtRAILEGE 536
Cdd:PLN03008  77 SDPYVTVVVPQA-TLARTRVLKNSQEPLWDEKFNISIAHPFA-YLEFQVKDDDVFGAQIIGTAKIPV-RDIASGE 148

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 38.57 E-value: 2.11e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKDI-IGKSDPYAVLYIRPLRNRTKKSKTI--NNDLNPIWNEHFEFIVEDAS--TQHLFVKVYDDEGL 338
Cdd:cd08393   17 LHVHVIQCQDLAAADPkKQRSDPYVKTYLLPDKSNRGKRKTSvkKKTLNPVFNETLRYKVEREElpTRVLNLSVWHRDSL 96

                         90       100
                 ....*....|....*....|....*...
gi 357478297 339 QSSELIGCTDIKLSELEPGKIKDVWLKL 366
Cdd:cd08393   97 GRNSFLGEVEVDLGSWDWSNTQPTWYPL 124

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. 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: 176011 [Multi-domain] Cd Length: 126 Bit Score: 37.64 E-value: 3.48e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 357478297 260 PVGILEVKLVQAKELTNKDIIGKSDPYAVLYIrplRNRTKKSKTINNDLNPIWNEHFEFIVEDASTQhLFVKVYDD 335
Cdd:cd04046    1 PQVVTQVHVHSAEGLSKQDSGGGADPYVIIKC---EGESVRSPVQKDTLSPEFDTQAIFYRKKPRSP-IKIQVWNS 72

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. 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: 176060 [Multi-domain] Cd Length: 126 Bit Score: 37.35 E-value: 4.86e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357478297 264 LEVKLVQAKELTNKdiIGKSDPYAVLYIR--PLRNrtkKSKTINNDLNPIWNEHFEFIVEDASTQHLFvKVYDDEGLQSS 341
Cdd:cd08678    1 LLVKNIKANGLSEA--AGSSNPYCVLEMDepPQKY---QSSTQKNTSNPFWDEHFLFELSPNSKELLF-EVYDNGKKSDS 74

                         90
                 ....*....|....
gi 357478297 342 ELIGCTDIKLSELE 355
Cdd:cd08678   75 KFLGLAIVPFDELR 88

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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.

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 36.65 E-value: 7.56e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 357478297 282 KSDPYAVLYIRPLRNRTKKSKTI--NNDLNPIWNEHFEFIV 320
Cdd:cd04029   36 RSNPYVKTYLLPDKSRQSKRKTSikRNTTNPVYNETLKYSI 76