NCBI Conserved Domain Search

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: 279.59 E-value: 3.71e-89

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 704 RGEMKLALQYVPEPVPGK---KLPTTGEVHIWVKECLDLPLLR-GSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFN 779
Cdd:cd04020     1 RGELKVALKYVPPESEGAlksKKPSTGELHVWVKEAKNLPALKsGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 780 HTMVYDGFRPEDLMEACVELTVWDHYKLT-NQFLGGLRIGFGTGKSYGTEVDWMDSTSEEVALWEKMVNSPNTWIEATLP 858
Cdd:cd04020    81 HTFVYDGVSPEDLSQACLELTVWDHDKLSsNDFLGGVRLGLGTGKSYGQAVDWMDSTGEEILLWQKMLDNPNSWVEGTLP 160


                  ..
gi 2028695509 859 LR 860
Cdd:cd04020   161 LR 162

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: 178.78 E-value: 1.66e-52

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKQRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFL 665
Cdd:cd08393    23 QCQDLAAADPKKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREELPTRVLNLSVWHRDSLGRNSFL 102

                          90       100
                  ....*....|....*....|....*.
gi 2028695509 666 GEVELDLETWDWDnkqNKQLRWYPLK 691
Cdd:cd08393   103 GEVEVDLGSWDWS---NTQPTWYPLQ 125

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: 139.31 E-value: 1.72e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKQRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFL 665
Cdd:cd08521    22 ECRNLAYADEKKKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHISKSQLETRTLQLSVWHHDRFGRNTFL 101

                          90       100
                  ....*....|....*....|....*
gi 2028695509 666 GEVELDLETWDWDNKQNKqlrWYPL 690
Cdd:cd08521   102 GEVEIPLDSWDLDSQQSE---WYPL 123

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: 125.24 E-value: 1.34e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKQRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFL 665
Cdd:cd04029    23 ECRNLAYGDEAKKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQLETRTLQLSVWHYDRFGRNTFL 102

                          90       100
                  ....*....|....*....|....*
gi 2028695509 666 GEVELDLETWDWDnkqNKQLRWYPL 690
Cdd:cd04029   103 GEVEIPLDSWNFD---SQHEECLPL 124

C2 domain first repeat present in Synaptotagmin-like protein 3; 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. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176038 [Multi-domain] Cd Length: 128 Bit Score: 104.14 E-value: 3.55e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 587 CKDLAAADVKKQRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFLG 666
Cdd:cd08392    24 CRNLAYGDEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADLLSSRQLQVSVWHSRTLKRRVFLG 103

                          90       100
                  ....*....|....*....|....*
gi 2028695509 667 EVELDLETWDWDNKQNKQLRWYPLK 691
Cdd:cd08392   104 EVLIPLADWDFEDTDSQRFLWYPLN 128

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: 91.20 E-value: 1.19e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 705 GEMKLALQYvpepvpgKKlpttGEVHIWVKECLDLPLLRGSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVY 784
Cdd:cd08381     2 GQVKLSISY-------KN----GTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVY 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2028695509 785 DGFRPEDLMEACVELTVWDHYKL-TNQFLGGLRIGFGTGKSYGTEVDW 831
Cdd:cd08381    71 DGLPVEDLQQRVLQVSVWSHDSLvENEFLGGVCIPLKKLDLSQETEKW 118

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: 75.36 E-value: 3.61e-16

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2028695509 738 DLPLLRGSHL-NSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVYDGFRPEDLMEACVELTVWDHYKL-TNQFLG 813
Cdd:cd04031    27 DLPPRDDGSLrNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRETLKERTLEVTVWDYDRDgENDFLG 104

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 73.89 E-value: 6.64e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 727 GEVHIWVKECLDLPLL-RGSHLNSFVKCTILpdtSRKSRQKTRAVGKTTNPIFNHTMVYDGFRPEDlmeACVELTVWDHY 805
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKdGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVPDPEN---AVLEIEVYDYD 74

                          90       100
                  ....*....|....*....|....*....
gi 2028695509 806 KLT-NQFLGGLRIGFGTGKSYGTEVDWMD 833
Cdd:pfam00168  75 RFGrDDFIGEVRIPLSELDSGEGLDGWYP 103

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: 73.48 E-value: 1.78e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 588 KDLAAADvkKQRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRY-KIEKQILKTQKLNLSIWHRDTFKRNSFLG 666
Cdd:cd08381    23 KNLPLLD--GSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYdGLPVEDLQQRVLQVSVWSHDSLVENEFLG 100

                          90       100
                  ....*....|....*....|....*
gi 2028695509 667 EVELDLETWDWDNKQNKqlrWYPLK 691
Cdd:cd08381   101 GVCIPLKKLDLSQETEK---WYPLG 122

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: 73.54 E-value: 2.32e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 707 MKLALQYVPEpvpgkklptTGEVHIWVKECLDL-PLLRGSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVYD 785
Cdd:cd08384     2 ILVSLMYNTQ---------RRGLIVGIIRCVNLaAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYD 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2028695509 786 gFRPEDLMEACVELTVWDH-YKLTNQFLGGLRIGfgtgksygtevdwMDSTSEEVALWEKMVNSPNTWIEA 855
Cdd:cd08384    73 -IKHSDLAKKTLEITVWDKdIGKSNDYIGGLQLG-------------INAKGERLRHWLDCLKNPDKKIEA 129

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 69.66 E-value: 2.67e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADvKKQRSDPYVKAYLLPDKGKmgkKKTLVVKKTLNPVYNEILRYKIEKQilKTQKLNLSIWHRDTFKRNSFL 665
Cdd:pfam00168   9 EAKNLPPKD-GNGTSDPYVKVYLLDGKQK---KKTKVVKNTLNPVWNETFTFSVPDP--ENAVLEIEVYDYDRFGRDDFI 82

                          90       100
                  ....*....|....*....|....*
gi 2028695509 666 GEVELDLETWDwdnKQNKQLRWYPL 690
Cdd:pfam00168  83 GEVRIPLSELD---SGEGLDGWYPL 104

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: 69.38 E-value: 5.86e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 704 RGEMKLALQYVPepvpgkklpTTGEVHIWVKECLDLPLLRGSHLNS--FVKCTILPDTSRKSRQKTRAVGKTTNPIFNHT 781
Cdd:cd08393     1 QGSVQFALDYDP---------KLRELHVHVIQCQDLAAADPKKQRSdpYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNET 71

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2028695509 782 MVYDgFRPEDLMEACVELTVWDHYKL-TNQFLGGLRIGFGTGKSYGTEVDW 831
Cdd:cd08393    72 LRYK-VEREELPTRVLNLSVWHRDSLgRNSFLGEVEVDLGSWDWSNTQPTW 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: 67.31 E-value: 2.65e-13

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2028695509 750 FVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVYDGFRPEDLMEACVELTVWDHYKLTNQFLGGLRI 817
Cdd:cd04035    39 YVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYGITEEDIQRKTLRLLVLDEDRFGNDFLGETRI 106

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: 66.50 E-value: 5.31e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 588 KDLAAADvKKQRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYK-IEKQILKTQKLNLSIWHRDTFKRNSFLG 666
Cdd:cd04031    26 RDLPPRD-DGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSnVRRETLKERTLEVTVWDYDRDGENDFLG 104

                          90       100
                  ....*....|....*....|....*
gi 2028695509 667 EVELDLETWDWDNkqnkQLRWYPLK 691
Cdd:cd04031   105 EVVIDLADALLDD----EPHWYPLQ 125

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: 65.17 E-value: 8.45e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKqRSDPYVKAYLLPDKgkmgKKKTLVVKKTLNPVYNEILRYKIEKqiLKTQKLNLSIWHRDTFKRNSFL 665
Cdd:cd00030     7 EARNLPAKDLNG-KSDPYVKVSLGGKQ----KFKTKVVKNTLNPVWNETFEFPVLD--PESDTLTVEVWDKDRFSKDDFL 79

                          90       100
                  ....*....|....*....|....*
gi 2028695509 666 GEVELDLETWDWDNKQNKQlrWYPL 690
Cdd:cd00030    80 GEVEIPLSELLDSGKEGEL--WLPL 102

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: 60.96 E-value: 2.42e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509  729 VHIWVKECLDLPLL-RGSHLNSFVKCTILPDTSRKsrQKTRAVGKTTNPIFNHTMVYDGFRPEDlmeACVELTVWDHYKL 807
Cdd:smart00239   2 LTVKIISARNLPPKdKGGKSDPYVKVSLDGDPKEK--KKTKVVKNTLNPVWNETFEFEVPPPEL---AELEIEVYDKDRF 76

                           90
                   ....*....|...
gi 2028695509  808 T-NQFLGGLRIGF 819
Cdd:smart00239  77 GrDDFIGQVTIPL 89

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: 61.30 E-value: 3.09e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 726 TGEVHIWVKECLDLPLL--RGSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVYDGFRPEdLMEACVELTVWD 803
Cdd:cd04029    14 TQSLNVHVKECRNLAYGdeAKKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQ-LETRTLQLSVWH 92

                          90       100       110
                  ....*....|....*....|....*....|
gi 2028695509 804 HYKLT-NQFLGGLRIGFGTGKSYGTEVDWM 832
Cdd:cd04029    93 YDRFGrNTFLGEVEIPLDSWNFDSQHEECL 122

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: 61.59 E-value: 3.24e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 587 CKDLAAADVKKQrSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFLG 666
Cdd:cd08384    22 CVNLAAMDANGY-SDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAKKTLEITVWDKDIGKSNDYIG 100

                          90       100
                  ....*....|....*....|...
gi 2028695509 667 EVELDLetwdwdNKQNKQLR-WY 688
Cdd:cd08384   101 GLQLGI------NAKGERLRhWL 117

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: 61.52 E-value: 3.37e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 600 SDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTF--KRNSFLGEVELDLETWDW 677
Cdd:cd04030    37 PDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEELKRRTLDVAVKNSKSFlsREKKLLGQVLIDLSDLDL 116

                          90
                  ....*....|....
gi 2028695509 678 DNKQNKqlrWYPLK 691
Cdd:cd04030   117 SKGFTQ---WYDLT 127

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: 60.35 E-value: 6.21e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 705 GEMKLALQYvpepvpgkKLPTTG-EVHIwvKECLDL----PLLRGShlNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFN 779
Cdd:cd08521     1 GEIEFSLSY--------NYKTGSlEVHI--KECRNLayadEKKKRS--NPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFN 68

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2028695509 780 HTMVYDgFRPEDLMEACVELTVWDHYKLT-NQFLG 813
Cdd:cd08521    69 ETLKYH-ISKSQLETRTLQLSVWHHDRFGrNTFLG 102

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: 59.90 E-value: 1.27e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 705 GEMKLALQYvpepvpgkkLPTTGEVHIWVKECLDLPLLRGS-HLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMV 783
Cdd:cd00276     1 GELLLSLSY---------LPTAERLTVVVLKARNLPPSDGKgLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFS 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2028695509 784 YDgFRPEDLMEACVELTVWDH-YKLTNQFLGGLRIGfgtgksygtevdwMDSTSEEVALWEKMVNSPN 850
Cdd:cd00276    72 FD-VPAEQLEEVSLVITVVDKdSVGRNEVIGQVVLG-------------PDSGGEELEHWNEMLASPR 125

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: 57.27 E-value: 1.00e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKQrSDPYVKAYLLPDKGKmgKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFL 665
Cdd:cd08385    24 QAADLPAMDMGGT-SDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFKVPYSELGNKTLVFSVYDFDRFSKHDLI 100

                          90
                  ....*....|..
gi 2028695509 666 GEVELDLETWDW 677
Cdd:cd08385   101 GEVRVPLLTVDL 112

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: 55.19 E-value: 2.38e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509  586 ECKDLAAADvKKQRSDPYVKAYLLPDKGKMGKKKTLVVKKtlNPVYNEILRYKIEKqiLKTQKLNLSIWHRDTFKRNSFL 665
Cdd:smart00239   8 SARNLPPKD-KGGKSDPYVKVSLDGDPKEKKKTKVVKNTL--NPVWNETFEFEVPP--PELAELEIEVYDKDRFGRDDFI 82


                   ....*....
gi 2028695509  666 GEVELDLET 674
Cdd:smart00239  83 GQVTIPLSD 91

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: 54.96 E-value: 6.69e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 725 TTGEVHIWVKECLDLPLLRGSHL-NSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVYDgFRPEDLMEA-CVEltVW 802
Cdd:cd04026    11 KDNKLTVEVREAKNLIPMDPNGLsDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFD-LKPADKDRRlSIE--VW 87

                          90
                  ....*....|....*..
gi 2028695509 803 DHYKLT-NQFLGGLRIG 818
Cdd:cd04026    88 DWDRTTrNDFMGSLSFG 104

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: 51.68 E-value: 4.41e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 729 VHIWVKECLDLPLL-RGSHLNSFVKCTILPdtsrKSRQKTRAVGKTTNPIFNHTMVydgFRPEDLMEACVELTVWDHYKL 807
Cdd:cd00030     1 LRVTVIEARNLPAKdLNGKSDPYVKVSLGG----KQKFKTKVVKNTLNPVWNETFE---FPVLDPESDTLTVEVWDKDRF 73

                          90       100
                  ....*....|....*....|....
gi 2028695509 808 T-NQFLGGLRIGFGTGKSYGTEVD 830
Cdd:cd00030    74 SkDDFLGEVEIPLSELLDSGKEGE 97

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: 51.90 E-value: 7.40e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 587 CKDLAAADVKKQrSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYK-IEKQILKTQKLNLSIWHRDTFkRNSFL 665
Cdd:cd04035    24 AKGLKAMDANGL-SDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYgITEEDIQRKTLRLLVLDEDRF-GNDFL 101


                  ....*..
gi 2028695509 666 GEVELDL 672
Cdd:cd04035   102 GETRIPL 108

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: 51.49 E-value: 9.72e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKQrSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTqKLNLSIWHRDTFKRNSFL 665
Cdd:cd04026    21 EAKNLIPMDPNGL-SDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKDR-RLSIEVWDWDRTTRNDFM 98


                  .
gi 2028695509 666 G 666
Cdd:cd04026    99 G 99

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: 51.25 E-value: 1.46e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 705 GEMKLALQYVPepvpgkklpTTGEVHIWVKECLDLPLLR-GSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMV 783
Cdd:cd08402     2 GDICFSLRYVP---------TAGKLTVVILEAKNLKKMDvGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFS 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2028695509 784 YDgFRPEDLMEACVELTVWDHYKL-TNQFLGGLRIGfgtGKSYGTEVD-WMD---STSEEVALWEKM 845
Cdd:cd08402    73 FE-VPFEQIQKVHLIVTVLDYDRIgKNDPIGKVVLG---CNATGAELRhWSDmlaSPRRPIAQWHTL 135

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: 50.72 E-value: 1.53e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 588 KDLAAADVKKQRSDPYVKAYLLPD---------KGKmgkkktlvvkkTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDT 658
Cdd:cd08390    24 RNLPPRTKDVAHCDPFVKVCLLPDerrslqskvKRK-----------TQNPNFDETFVFQVSFKELQRRTLRLSVYDVDR 92

                          90       100
                  ....*....|....*....|....
gi 2028695509 659 FKRNSFLGEVELDLETWDWDNKQN 682
Cdd:cd08390    93 FSRHCIIGHVLFPLKDLDLVKGGV 116

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: 50.73 E-value: 1.80e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 704 RGEMKLALQYVpepVPGKKLPTTgeVHiwvkECLDLPLLRGSHL-NSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTM 782
Cdd:cd04030     2 LGRIQLTIRYS---SQRQKLIVT--VH----KCRNLPPCDSSDIpDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETF 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2028695509 783 VYDgFRPEDLMEACVELTVWDHYKLT---NQFLGGLRIGFGT 821
Cdd:cd04030    73 EFP-VSLEELKRRTLDVAVKNSKSFLsreKKLLGQVLIDLSD 113

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: 50.02 E-value: 2.93e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 600 SDPYVKAYLLPDKG-KMgkkKTLVVKKTLNPVYNEILRYK---IEKqiLKTQKLNLSIWHRDTFKRNSFLGEVELDLETW 675
Cdd:cd08386    37 SDPFVKIYLLPDKKhKL---ETKVKRKNLNPHWNETFLFEgfpYEK--LQQRVLYLQVLDYDRFSRNDPIGEVSLPLNKV 111

                          90
                  ....*....|....*..
gi 2028695509 676 DWdnkQNKQLRWYPLKR 692
Cdd:cd08386   112 DL---TEEQTFWKDLKP 125

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: 49.50 E-value: 5.26e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 705 GEMKLALQYvpepvpgkkLPTTGEVH---IWVKECLDLPLLRGShlNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHT 781
Cdd:cd08410     1 GELLLSLNY---------LPSAGRLNvdiIRAKQLLQTDMSQGS--DPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNES 69

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2028695509 782 MVYDgFRPEDLMEACVELTVWDH-YKLTNQFLGGLRIG-FGTGKSygtevdwmdstseEVALWEKMVNSPNTWIE 854
Cdd:cd08410    70 FSFK-VPQEELENVSLVFTVYGHnVKSSNDFIGRIVIGqYSSGPS-------------ETNHWRRMLNSQRTAVE 130

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: 48.55 E-value: 1.33e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKQrSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFL 665
Cdd:cd08402    23 EAKNLKKMDVGGL-SDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQIQKVHLIVTVLDYDRIGKNDPI 101


                  ....*
gi 2028695509 666 GEVEL 670
Cdd:cd08402   102 GKVVL 106

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: 48.12 E-value: 1.69e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKQRSDPYVKAYLLPDKGKmgKKKTLVVKKTLNPVYNEILR-YKIEKQILKTQKLNLSIWHRDTFKRNSF 664
Cdd:cd08388    24 ECRDLPAMDEQSGTSDPYVKLQLLPEKEH--KVKTRVLRKTRNPVYDETFTfYGIPYNQLQDLSLHFAVLSFDRYSRDDV 101


                  ....
gi 2028695509 665 LGEV 668
Cdd:cd08388   102 IGEV 105

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: 47.96 E-value: 1.79e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKQrSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFL 665
Cdd:cd00276    22 KARNLPPSDGKGL-SDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLEEVSLVITVVDKDSVGRNEVI 100


                  ....*....
gi 2028695509 666 GEVELDLET 674
Cdd:cd00276   101 GQVVLGPDS 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: 47.35 E-value: 2.88e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2028695509 733 VKECLDLPLLRGSHLNS--FVKCTILPDtsRKSRQKTRAVGKTTNPIFNHTMVYDGFRPEDLMEACVELTV--WDHY 805
Cdd:cd08388    22 IIECRDLPAMDEQSGTSdpYVKLQLLPE--KEHKVKTRVLRKTRNPVYDETFTFYGIPYNQLQDLSLHFAVlsFDRY 96

FYVE-type zinc finger; This FYVE-type zinc finger is found at the N-terminus of effector proteins including rabphilin-3A and regulating synaptic membrane exocytosis protein 2.

Pssm-ID: 426716 Cd Length: 118 Bit Score: 45.83 E-value: 7.50e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2028695509   5 SFLTEEEQEAIMKVLQRDAALKRAEEERVRHLPEKIKDDQQLKNMSG 51
Cdd:pfam02318   1 SKLTDEEAEHVWEVVQRDFDLRKKEEERLGELKGKLDKESSKRELLG 47

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: 46.62 E-value: 8.20e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 729 VHIWVKECLDLPLLRGShLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVYDGFRP------------EDLMEAC 796
Cdd:cd04010     2 LSVRVIECSDLALKNGT-CDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVTIDsspekkqfempeEDAEKLE 80

                          90       100
                  ....*....|....*....|..
gi 2028695509 797 VELTVWDHYKLTNQ-FLGGLRI 817
Cdd:cd04010    81 LRVDLWHASMGGGDvFLGEVRI 102

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: 45.78 E-value: 8.72e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2028695509 730 HIWVKECLDLPL--LRGSHlNSFVKCTILPDtsRKSRQKTRAVGKTTNPIFNHTMVYDGFRPEDLMEACVELTVWDH 804
Cdd:cd08386    19 TLKILKAVELPAkdFSGTS-DPFVKIYLLPD--KKHKLETKVKRKNLNPHWNETFLFEGFPYEKLQQRVLYLQVLDY 92

C2 domain second repeat present in Synaptotagmin 15; 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. 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: 176054 [Multi-domain] Cd Length: 137 Bit Score: 45.79 E-value: 1.04e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 704 RGEMKLALQYvpepvpgkkLPTTGEVHIWVKECLDLPLLRGSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMV 783
Cdd:cd08409     1 LGDIQISLTY---------NPTLNRLTVVVLRARGLRQLDHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFS 71

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2028695509 784 YdGFRPEDLMEACVELTVWDH-----YKLtnqfLGGLRIGfgtgksygtevDWMDSTSEEVALWEKMVNSPNTWIE 854
Cdd:cd08409    72 F-KVTSRQLDTASLSLSVMQSggvrkSKL----LGRVVLG-----------PFMYARGKELEHWNDMLSKPKELIK 131

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: 45.58 E-value: 1.27e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 705 GEMKLALQYvpepvpgkkLPTTGEVHIWVKECLDLP---LLRGShlNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHT 781
Cdd:cd08403     1 GELMFSLCY---------LPTAGRLTLTIIKARNLKamdITGFS--DPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEA 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2028695509 782 MVYDgFRPEDLMEACVELTVWDHYKL-TNQFLGGLRIG---FGTGKSYGTEVdwMDSTSEEVALW 842
Cdd:cd08403    70 LVFD-VPPENVDNVSLIIAVVDYDRVgHNELIGVCRVGpnaDGQGREHWNEM--LANPRKPIAQW 131

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: 44.67 E-value: 2.57e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 729 VHIWVKECLDLPLLRGSHLNSFVKCTILpDTSRKSRQKTRAVGKTTNPIFNHTMVYDGFRP------------EDLMEAC 796
Cdd:cd08675     1 LSVRVLECRDLALKSNGTCDPFARVTLN-YSSKTDTKRTKVKKKTNNPRFDEAFYFELTIGfsyekksfkveeEDLEKSE 79

                          90       100
                  ....*....|....*....|..
gi 2028695509 797 VELTVWDHYKLT-NQFLGGLRI 817
Cdd:cd08675    80 LRVELWHASMVSgDDFLGEVRI 101

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: 43.96 E-value: 4.70e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 704 RGEMKLALQYvpepvpgkkLPTTGEVHIWVKECLDLPLLRGSHL-NSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTM 782
Cdd:cd08404     1 RGELLLSLCY---------QPTTNRLTVVVLKARHLPKMDVSGLaDPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESF 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2028695509 783 VYDgfRPEDLME-ACVELTVWDHYKLT-NQFLGGLRIGfgtGKSYGTEVDWM----DSTSEEVALWEKM 845
Cdd:cd08404    72 VFD--IPSEELEdISVEFLVLDSDRVTkNEVIGRLVLG---PKASGSGGHHWkevcNPPRRQIAEWHML 135

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the 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: 176067 [Multi-domain] Cd Length: 119 Bit Score: 43.60 E-value: 4.87e-05

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2028695509 748 NSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVYD 785
Cdd:cd08685    33 NSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFD 70

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: 43.55 E-value: 6.05e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKQrSDPYVKAYLLPDKGKMgkKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFL 665
Cdd:cd08387    24 QARNLQPRDFSGT-ADPYCKVRLLPDRSNT--KQSKIHKKTLNPEFDESFVFEVPPQELPKRTLEVLLYDFDQFSRDECI 100

                          90       100
                  ....*....|....*....|....*..
gi 2028695509 666 GEVELDLETWDWDNKqnKQLrWYPLKR 692
Cdd:cd08387   101 GVVELPLAEVDLSEK--LDL-WRKIQS 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: 43.57 E-value: 6.16e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADV-KKQRSDPYVKAYLLPDKGKmgkkkTLVVKKTLNPVYNEilRYKIEKQILKTQKLNLSIWHRDTFKRNSF 664
Cdd:cd04024     9 EAKDLAAKDRsGKGKSDPYAILSVGAQRFK-----TQTIPNTLNPKWNY--WCEFPIFSAQNQLLKLILWDKDRFAGKDY 81

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2028695509 665 LGEVELDLETWDWDNKQNKQLRWYPLKRKTAP 696
Cdd:cd04024    82 LGEFDIALEEVFADGKTGQSDKWITLKSTRPG 113

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: 41.53 E-value: 2.32e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2028695509 764 RQKTRAVGKTTNPIFNHTMVydgFRPEDLMEACVELTVWDHYKLTNQFLGGLRI 817
Cdd:cd08378    29 KGSTKAIERTSNPEWNQVFA---FSKDRLQGSTLEVSVWDKDKAKDDFLGGVCF 79

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: 41.10 E-value: 3.53e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 703 NRGEMKLALQYVPEpvpgkklptTGEVHIWVKECLDLPLLR-GSHLNSFVKCTILPDtsRKSRQKTRAVGKTTNPIFNHT 781
Cdd:cd08385     1 KLGKLQFSLDYDFQ---------SNQLTVGIIQAADLPAMDmGGTSDPYVKVYLLPD--KKKKFETKVHRKTLNPVFNET 69

                          90       100
                  ....*....|....*....|...
gi 2028695509 782 MVYDgFRPEDLMEACVELTVWDH 804
Cdd:cd08385    70 FTFK-VPYSELGNKTLVFSVYDF 91

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: 41.37 E-value: 3.63e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2028695509 743 RGSHLNSFVKCTIL-PDTSRKSRQKTRAV-GKTTNPIFNHTMVYDGFRPEdLmeACVELTVWDHYKLTNQFLG 813
Cdd:cd00275    21 KGSIVDPYVEVEIHgLPADDSAKFKTKVVkNNGFNPVWNETFEFDVTVPE-L--AFLRFVVYDEDSGDDDFLG 90

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: 41.25 E-value: 4.68e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAADVKKqRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFL 665
Cdd:cd08405    23 KARNLKAMDING-TSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERLRETTLIITVMDKDRLSRNDLI 101

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2028695509 666 GEVEL-----DLETWDWDNKQNKQ----LRWYPLK 691
Cdd:cd08405   102 GKIYLgwksgGLELKHWKDMLSKPrqpvAQWHRLK 136

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: 41.16 E-value: 4.73e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 588 KDLAAADVKKqrSDPYVKAYLLPDKGKMGKKKTLVvkktlNPVYNEILRYKIEKqilKTQKLNLSIWHRDTFKRNSFLGE 667
Cdd:cd04038    12 TNLAVRDFTS--SDPYVVLTLGNQKVKTRVIKKNL-----NPVWNEELTLSVPN---PMAPLKLEVFDKDTFSKDDSMGE 81


                  ....*.
gi 2028695509 668 VELDLE 673
Cdd:cd04038    82 AEIDLE 87

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: 40.95 E-value: 5.00e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 587 CKDLAAADVKKqRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFLG 666
Cdd:cd08403    23 ARNLKAMDITG-FSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVDNVSLIIAVVDYDRVGHNELIG 101

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2028695509 667 EVE-------LDLETWD--WDNKQNKQLRWYPL 690
Cdd:cd08403   102 VCRvgpnadgQGREHWNemLANPRKPIAQWHQL 134

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: 40.25 E-value: 6.36e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 729 VHIWVKECLDLPllrGSHLNSFVKCTILpDTSRKSRQKTRavgkTTNPIFNHTMVYDgFR--PEDLMEACVELTVWDHYK 806
Cdd:cd04011     6 VRVRVIEARQLV---GGNIDPVVKVEVG-GQKKYTSVKKG----TNCPFYNEYFFFN-FHesPDELFDKIIKISVYDSRS 76

                          90
                  ....*....|....*.
gi 2028695509 807 L-TNQFLGGLRIGFGT 821
Cdd:cd04011    77 LrSDTLIGSFKLDVGT 92

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: 40.48 E-value: 9.15e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 704 RGEMKLALQYVPepvpgkklpTTGEVHIWVKECLDLPL--LRGSHlNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHT 781
Cdd:cd08405     1 RGELLLSLCYNP---------TANRITVNIIKARNLKAmdINGTS-DPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNES 70

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2028695509 782 MVYDgFRPEDLMEACVELTVWDHYKLT-NQFLGGLRIGFGTGKSygtevdwmdstseEVALWEKMVNSPNT 851
Cdd:cd08405    71 FIFN-IPLERLRETTLIITVMDKDRLSrNDLIGKIYLGWKSGGL-------------ELKHWKDMLSKPRQ 127

C2 domain first repeat present in Synaptotagmin-like protein 3; 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. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176038 [Multi-domain] Cd Length: 128 Bit Score: 39.81 E-value: 1.06e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 705 GEMKLALQYVPEpvpgkklptTGEVHIWVKECLDLPL--LRGSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTM 782
Cdd:cd08392     2 GEIEFALHYNFR---------TSCLEITIKACRNLAYgdEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETL 72

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2028695509 783 VYDgFRPEDLMEACVELTVWDHYKLTNQ-FLG 813
Cdd:cd08392    73 KYV-VEADLLSSRQLQVSVWHSRTLKRRvFLG 103

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: 38.44 E-value: 2.13e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 729 VHIWVKECLDLPLL-RGSHL-NSFVKCTILPDTsrksrQKTRAVGKTTNPIFNHtmvyDGFR----PEDLMEACVELTVW 802
Cdd:cd08688     1 LKVRVVAARDLPVMdRSSDLtDAFVEVKFGSTT-----YKTDVVKKSLNPVWNS----EWFRfevdDEELQDEPLQIRVM 71


                  ..
gi 2028695509 803 DH 804
Cdd:cd08688    72 DH 73

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: 38.81 E-value: 2.38e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 586 ECKDLAAAD-----VKKQRSDPYVKAYLLPDKGKmgkkkTLVVKKTLNPVYNEIlrYKIEKQILKTQKLNLSIWHRDTFK 660
Cdd:cd08391     9 EAQDLVAKDkfvggLVKGKSDPYVIVRVGAQTFK-----SKVIKENLNPKWNEV--YEAVVDEVPGQELEIELFDEDPDK 81

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2028695509 661 rNSFLGEVELDLETWDwdnKQNKQLRWYPLK 691
Cdd:cd08391    82 -DDFLGRLSIDLGSVE---KKGFIDEWLPLE 108

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: 39.14 E-value: 2.42e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 738 DLPLLRGSHLN-SFVKCTILPDT--SRKSRQKTRAVGKTTNPIFNHTMVYDgFRPEDLME--ACVELTVWDHYKL-TNQF 811
Cdd:cd04009    27 NLLPLDSNGSSdPFVKVELLPRHlfPDVPTPKTQVKKKTLFPLFDESFEFN-VPPEQCSVegALLLFTVKDYDLLgSNDF 105


                  ..
gi 2028695509 812 LG 813
Cdd:cd04009   106 EG 107

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: 38.33 E-value: 3.82e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 588 KDLAAADVKkQRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWHRDTFKRNSFLGE 667
Cdd:cd08410    24 KQLLQTDMS-QGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEELENVSLVFTVYGHNVKSSNDFIGR 102


                  .
gi 2028695509 668 V 668
Cdd:cd08410   103 I 103

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: 38.20 E-value: 4.72e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509 629 PVYNEILRYKIEKQILKTQK---LNLSIWHRDTFKRNSFLGEVELDLETWDwDNKQNKQLRWYPLKRKTAPvalEAENRG 705
Cdd:cd08682    44 PVWKEECSFELPGLLSGNGNratLQLTVMHRNLLGLDKFLGQVSIPLNDLD-EDKGRRRTRWFKLESKPGK---DDKERG 119


                  ....*..
gi 2028695509 706 EMKLALQ 712
Cdd:cd08682   120 EIEVDIQ 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: 37.32 E-value: 8.91e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2028695509 764 RQKTRAVGKTTNPIFNHTMVYDGFRPEDLMEACVELTVWDHYKLTN--QFLGGLRIGFGTGKSYGTEV 829
Cdd:cd04022    33 KKRTRTKPKDLNPVWNEKLVFNVSDPSRLSNLVLEVYVYNDRRSGRrrSFLGRVRISGTSFVPPSEAV 100

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 39.74 E-value: 8.92e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509  628 NPVYNEILRYKIEKQilkTQKLNLSIWHRDTFKRNSFLGEVELDLETWDWDNKQNKQLrwYPLKRKTAPValeaenrGEM 707
Cdd:COG5038    483 NPVWNETFYILLNSF---TDPLNLSLYDFNSFKSDKVVGSTQLDLALLHQNPVKKNEL--YEFLRNTKNV-------GRL 550

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2028695509  708 KLALQYVPEpVPGKKLP----------TTGEVHIWVKECLDLPLLRGSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPI 777
Cdd:COG5038    551 TYDLRFFPV-IEDKKELkgsvepledsNTGILKVTLREVKALDELSSKKDNKSAELYTNAKEVYSTGKLKFTNHPSWNLQ 629


                   ...
gi 2028695509  778 FNH 780
Cdd:COG5038    630 YNV 632