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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  20 VQVTVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLgAPVWREEATFELPPLLSsgaAPAAAATLQLTVLHRAL 99
Cdd:cd08682    1 VQVTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTT-SPVWKEECSFELPGLLS---GNGNRATLQLTVMHRNL 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 297206826 100 LGLDKFLGRAEVDLRELHRDQGRRKKQWYTLKSKPGKKDKERGEIEVDIQ 149
Cdd:cd08682   77 LGLDKFLGQVSIPLNDLDEDKGRRRTRWFKLESKPGKDDKERGEIEVDIQ 126

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  20 VQVTVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLgAPVWREEATFELPPLLSsgaAPAAAATLQLTVLHRAL 99
Cdd:cd08682    1 VQVTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTT-SPVWKEECSFELPGLLS---GNGNRATLQLTVMHRNL 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 297206826 100 LGLDKFLGRAEVDLRELHRDQGRRKKQWYTLKSKPGKKDKERGEIEVDIQ 149
Cdd:cd08682   77 LGLDKFLGQVSIPLNDLDEDKGRRRTRWFKLESKPGKDDKERGEIEVDIQ 126

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826    22 VTVLQARGLRAKGPGGTSDAYAVIQVG---KEKYATSVSERSLgAPVWREEATFELPPLLSSgaapaaaaTLQLTVLHRA 98
Cdd:smart00239   4 VKIISARNLPPKDKGGKSDPYVKVSLDgdpKEKKKTKVVKNTL-NPVWNETFEFEVPPPELA--------ELEIEVYDKD 74

                           90       100
                   ....*....|....*....|....*.
gi 297206826    99 LLGLDKFLGRAEVDLRELHRDQGRRK 124
Cdd:smart00239  75 RFGRDDFIGQVTIPLSDLLLGGRHEK 100

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  20 VQVTVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLgAPVWREEATFELPPLLSsgaAPAAAATLQLTVLHRAL 99
Cdd:cd08682    1 VQVTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTT-SPVWKEECSFELPGLLS---GNGNRATLQLTVMHRNL 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 297206826 100 LGLDKFLGRAEVDLRELHRDQGRRKKQWYTLKSKPGKKDKERGEIEVDIQ 149
Cdd:cd08682   77 LGLDKFLGQVSIPLNDLDEDKGRRRTRWFKLESKPGKDDKERGEIEVDIQ 126

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  20 VQVTVLQARGLRAKGPGGTSDAYAVIQVG-KEKYATSVSERSLgAPVWREEATFELPPLLSSgaapaaaaTLQLTVLHRA 98
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGgKQKFKTKVVKNTL-NPVWNETFEFPVLDPESD--------TLTVEVWDKD 71

                         90       100       110
                 ....*....|....*....|....*....|..
gi 297206826  99 LLGLDKFLGRAEVDLRELhRDQGRRKKQWYTL 130
Cdd:cd00030   72 RFSKDDFLGEVEIPLSEL-LDSGKEGELWLPL 102

FIP domain; The FIP domain is the Rab11-binding domain (RBD) at the C-terminus of a family of Rab11-interacting proteins (FIPs). The Rab proteins constitute the largest family of small GTPases (>60 members in mammals). Among them Rab11 is a well characterized regulator of endocytic and recycling pathways. Rab11 associates with a broad range of post-Golgi organelles, including recycling endosomes.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 297206826  588 THDELIQLVLKQKETIskkefqvRELEDYIDNLLVRVMEETPNILRVP 635
Cdd:pfam09457   1 SRDELQDALQKQEEEN-------RRLEDYIDNILLRIMEHNPSILEVP 41

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  22 VTVLQARGLRAK--GPGGTSDAYAVIQVGKEKYATSVSERSLGaPVWREEATFelpPLLSSGAAPaaaatLQLTVLHRAL 99
Cdd:cd04024    5 VHVVEAKDLAAKdrSGKGKSDPYAILSVGAQRFKTQTIPNTLN-PKWNYWCEF---PIFSAQNQL-----LKLILWDKDR 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 297206826 100 LGLDKFLGRAEVDLREL-HRDQGRRKKQWYTLKSK-PGKKDKERGEIEV 146
Cdd:cd04024   76 FAGKDYLGEFDIALEEVfADGKTGQSDKWITLKSTrPGKTSVVSGEIHL 124

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  22 VTVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLGAPVWREEATFELPPllssgaapAAAATLQLTVLH---RA 98
Cdd:cd08681    5 VVVLKARNLPNKRKLDKQDPYCVLRIGGVTKKTKTDFRGGQHPEWDEELRFEITE--------DKKPILKVAVFDddkRK 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 297206826  99 llglDKFLGRAEVDLRE-LHRDQgrrKKQWYTLKSKPgkkdKERGEIEVDIQF 150
Cdd:cd08681   77 ----PDLIGDTEVDLSPaLKEGE---FDDWYELTLKG----RYAGEVYLELTF 118

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  23 TVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLgAPVWREEATFELPPLLSSgaapaaaaTLQLTVLHRALLGL 102
Cdd:cd04025    5 HVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSC-YPRWNEVFEFELMEGADS--------PLSVEVWDWDLVSK 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 297206826 103 DKFLGRAEVDLRELHrdQGRRKKQWYTLKSKPGKKDKERGEI 144
Cdd:cd04025   76 NDFLGKVVFSIQTLQ--QAKQEEGWFRLLPDPRAEEESGGNL 115

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  19 HVQVTVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLGaPVWREEATFELPPLLSsgaapaaaaTLQLTVLHRA 98
Cdd:cd08377    2 FLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLN-PEWNKIFTFPIKDIHD---------VLEVTVYDED 71

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 297206826  99 LLGLDKFLGRAEVDLreLHRDQGRRKkqWYTLKSKpGKKDKERGEI--EVDIQ 149
Cdd:cd08377   72 KDKKPEFLGKVAIPL--LSIKNGERK--WYALKDK-KLRTRAKGSIllEMDVI 119

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 297206826  20 VQVTVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLGaPVWREEATFE 73
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLN-PVWNEKFHFE 55

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  19 HVQVTVLQARGLRAKGpggTSDAYAVIQVGKEKYA-TSVSERSlgAPVWREEATFELPPLLSSgaapaaAATLQLTVLHR 97
Cdd:cd08383    1 SLRLRILEAKNLPSKG---TRDPYCTVSLDQVEVArTKTVEKL--NPFWGEEFVFDDPPPDVT------FFTLSFYNKDK 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 297206826  98 ALLGLDKFLGRaeVDLRELhrDQGRRKKQWYTLKSKPGKKDkERGEIEVDIQF 150
Cdd:cd08383   70 RSKDRDIVIGK--VALSKL--DLGQGKDEWFPLTPVDPDSE-VQGSVRLRARY 117

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  20 VQVTVLQARGLRAKGPGGTSDAYAVIQV-GKEKYATSVSERSLGAPVWREEATFELPPLLSSGaapaAAATLQLTVLHRA 98
Cdd:cd04051    2 LEITIISAEDLKNVNLFGKMKVYAVVWIdPSHKQSTPVDRDGGTNPTWNETLRFPLDERLLQQ----GRLALTIEVYCER 77

                         90
                 ....*....|....*...
gi 297206826  99 LLGLDKFLGRAEVDLREL 116
Cdd:cd04051   78 PSLGDKLIGEVRVPLKDL 95

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  22 VTVLQARGLrakgPGGTSDAYAVIQVGKEKYATSVSERSLgAPVWREEATFELPPLLSSgaapaaaaTLQLTVlHRALLG 101
Cdd:cd08378    4 VRVVKARGL----PANSNDPVVEVKLGNYKGSTKAIERTS-NPEWNQVFAFSKDRLQGS--------TLEVSV-WDKDKA 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 297206826 102 LDKFLGRAEVDLRELH-RDQ--GRRKKQWYTLKSKPGKKDkeRGEIEVDIQF 150
Cdd:cd08378   70 KDDFLGGVCFDLSEVPtRVPpdSPLAPQWYRLEDKKGGRV--GGELMLAVWF 119

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  14 MWSPTH--VQVTVLQARGLRAKGPGGTSDAYAVIQV---GK--EKYATSVSERSLGaPVWREEATFELPpllssgAAPAA 86
Cdd:cd08405    9 CYNPTAnrITVNIIKARNLKAMDINGTSDPYVKVWLmykDKrvEKKKTVIKKRTLN-PVFNESFIFNIP------LERLR 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 297206826  87 AATLQLTVLHRALLGLDKFLGRAEVDlrelHRDQGRRKKQWYTLKSKPGK 136
Cdd:cd08405   82 ETTLIITVMDKDRLSRNDLIGKIYLG----WKSGGLELKHWKDMLSKPRQ 127

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  20 VQVTVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLGaPVWREEATFELppllssgAAPAAAATLQltVLHRAL 99
Cdd:cd04046    5 TQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLS-PEFDTQAIFYR-------KKPRSPIKIQ--VWNSNL 74

                         90       100       110
                 ....*....|....*....|....*....|....
gi 297206826 100 LgLDKFLGRAEV-----DLRELH----RDQGRRK 124
Cdd:cd04046   75 L-CDEFLGQATLsadpnDSQTLRtlplRKRGRDA 107

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  21 QVTVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLGAPVWREEATFELPpllSSGAAPAAAatLQLTVLHRALL 100
Cdd:cd04049    4 EVLLISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAKGDGRNPEWNEKFKFTVE---YPGWGGDTK--LILRIMDKDNF 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 297206826 101 GLDKFLGRAEVDLRELHrDQGRRkKQWYTLKSKP----GKKDKERGEI 144
Cdd:cd04049   79 SDDDFIGEATIHLKGLF-EEGVE-PGTAELVPAKynvvLEDDTYKGEI 124

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  21 QVTVLQARGLRAKGPGGTSDAYAVIQV-------GKEKYATSVSERSLgAPVWREEATFELPPLLSSgaapAAAATLQLT 93
Cdd:cd04009   19 RVEILNARNLLPLDSNGSSDPFVKVELlprhlfpDVPTPKTQVKKKTL-FPLFDESFEFNVPPEQCS----VEGALLLFT 93

                         90       100
                 ....*....|....*....|...
gi 297206826  94 VLHRALLGLDKFLGRAEVDLREL 116
Cdd:cd04009   94 VKDYDLLGSNDFEGEAFLPLNDI 116

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  24 VLQARGLRAKGPGGTSDAYAVIQVGKEKYA-TSVSERSLgAPVWREEATFELPPLLssgaapaaaATLQLTVLHRALLGL 102
Cdd:cd04054    6 IVEGKNLPAKDITGSSDPYCIVKVDNEVIIrTATVWKTL-NPFWGEEYTVHLPPGF---------HTVSFYVLDEDTLSR 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 297206826 103 DKFLGRAEVDlRELHRDQGRRKKQWYTLksKPGKKDKE-RGEIEVDIQ 149
Cdd:cd04054   76 DDVIGKVSLT-REVISAHPRGIDGWMNL--TEVDPDEEvQGEIHLELS 120

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  20 VQVTVLQARGLRAKGPGGTSDAYAVIQVGKEKYATSVSERSLGAPVWREEATF---ElpPLlssgaapaaAATLQLTVLH 96
Cdd:cd04019    2 LRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPSQTRNGNPSWNEELMFvaaE--PF---------EDHLILSVED 70

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 297206826  97 RALLGLDKFLGRAEVDLRELHRDQGRRK--KQWYTLK-----SKPGKKDKERGEIEVDI 148
Cdd:cd04019   71 RVGPNKDEPLGRAVIPLNDIERRVDDRPvpSRWFSLErpggaMEQKKKRKFASRIHLRL 129

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  22 VTVLQARGLRAKGPGGTSDAYAVIQV-GKEKYATSVSERSLGaPVWREEATFELPPLlssgaapaaAATLQLTVLHRALL 100
Cdd:cd04042    4 IHLKEGRNLAARDRGGTSDPYVKFKYgGKTVYKSKTIYKNLN-PVWDEKFTLPIEDV---------TQPLYIKVFDYDRG 73

                         90
                 ....*....|....*.
gi 297206826 101 GLDKFLGRAEVDLREL 116
Cdd:cd04042   74 LTDDFMGSAFVDLSTL 89

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  20 VQVTVLQARGLrakgPGGTSDAYAVIQVGKEKYATSVSERSLgAPVWREEATFE--LPPLlssgaaPAAAATLQLTVLHR 97
Cdd:cd04011    6 VRVRVIEARQL----VGGNIDPVVKVEVGGQKKYTSVKKGTN-CPFYNEYFFFNfhESPD------ELFDKIIKISVYDS 74

                         90
                 ....*....|....*.
gi 297206826  98 ALLGLDKFLGRAEVDL 113
Cdd:cd04011   75 RSLRSDTLIGSFKLDV 90

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297206826  22 VTVLQARGLRAKGPGGTSDAYAVI---QVGKEKYATSVSERSLGaPVWREEATFELPPLLSSgaapaaaaTLQLTVLHRA 98
Cdd:cd04043    5 IRIVRAENLKADSSNGLSDPYVTLvdtNGKRRIAKTRTIYDTLN-PRWDEEFELEVPAGEPL--------WISATVWDRS 75

                         90
                 ....*....|....*
gi 297206826  99 LLGLDKFLGRAEVDL 113
Cdd:cd04043   76 FVGKHDLCGRASLKL 90