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 24308075  21 VQVTVLRARGLRGKssGAGSTSDAYTVIQVGREKYSTSVVEKThGCPEWREECSFELPPGALDGLLRaqeadagpapwaa 100
Cdd:cd08682   1 VQVTVLQARGLLCK--GKSGTNDAYVIIQLGKEKYSTSVKEKT-TSPVWKEECSFELPGLLSGNGNR------------- 64

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24308075 101 ssaaaCELVLTTMHRSLIGVDKFLGQATVALDEVFGAGRAQHTQWYKLHSKPGKKEKERGEIEVTIQ 167
Cdd:cd08682  65 -----ATLQLTVMHRNLLGLDKFLGQVSIPLNDLDEDKGRRRTRWFKLESKPGKDDKERGEIEVDIQ 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 24308075  21 VQVTVLRARGLRGKssGAGSTSDAYTVIQVGREKYSTSVVEKThGCPEWREECSFELPPGALDGLLRaqeadagpapwaa 100
Cdd:cd08682   1 VQVTVLQARGLLCK--GKSGTNDAYVIIQLGKEKYSTSVKEKT-TSPVWKEECSFELPGLLSGNGNR------------- 64

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24308075 101 ssaaaCELVLTTMHRSLIGVDKFLGQATVALDEVFGAGRAQHTQWYKLHSKPGKKEKERGEIEVTIQ 167
Cdd:cd08682  65 -----ATLQLTVMHRNLLGLDKFLGQVSIPLNDLDEDKGRRRTRWFKLESKPGKDDKERGEIEVDIQ 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 24308075     23 VTVLRARGLRGKSSGagSTSDAYTVIQVG---REKYSTSVVEKThGCPEWREECSFELPPGALDgllraqeadagpapwa 99
Cdd:smart00239   4 VKIISARNLPPKDKG--GKSDPYVKVSLDgdpKEKKKTKVVKNT-LNPVWNETFEFEVPPPELA---------------- 64

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 24308075    100 assaaacELVLTTMHRSLIGVDKFLGQATVALDEVFGAGRAQH 142
Cdd:smart00239  65 -------ELEIEVYDKDRFGRDDFIGQVTIPLSDLLLGGRHEK 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 24308075  21 VQVTVLRARGLRGKssGAGSTSDAYTVIQVGREKYSTSVVEKThGCPEWREECSFELPPGALDGLLRaqeadagpapwaa 100
Cdd:cd08682   1 VQVTVLQARGLLCK--GKSGTNDAYVIIQLGKEKYSTSVKEKT-TSPVWKEECSFELPGLLSGNGNR------------- 64

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24308075 101 ssaaaCELVLTTMHRSLIGVDKFLGQATVALDEVFGAGRAQHTQWYKLHSKPGKKEKERGEIEVTIQ 167
Cdd:cd08682  65 -----ATLQLTVMHRNLLGLDKFLGQVSIPLNDLDEDKGRRRTRWFKLESKPGKDDKERGEIEVDIQ 126

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308075    20 HVQVTVLRARGLRGKSSGagSTSDAYTVIQV--GREKYSTSVVEKThGCPEWREECSFELPPgaldgllraqeadagpap 97
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGN--GTSDPYVKVYLldGKQKKKTKVVKNT-LNPVWNETFTFSVPD------------------ 60

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 24308075    98 waassAAACELVLTTMHRSLIGVDKFLGQATVALDEVFgaGRAQHTQWYKL 148
Cdd:pfam00168  61 -----PENAVLEIEVYDYDRFGRDDFIGEVRIPLSELD--SGEGLDGWYPL 104

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 24308075     23 VTVLRARGLRGKSSGagSTSDAYTVIQVG---REKYSTSVVEKThGCPEWREECSFELPPGALDgllraqeadagpapwa 99
Cdd:smart00239   4 VKIISARNLPPKDKG--GKSDPYVKVSLDgdpKEKKKTKVVKNT-LNPVWNETFEFEVPPPELA---------------- 64

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 24308075    100 assaaacELVLTTMHRSLIGVDKFLGQATVALDEVFGAGRAQH 142
Cdd:smart00239  65 -------ELEIEVYDKDRFGRDDFIGQVTIPLSDLLLGGRHEK 100

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 24308075   601 THDELISLLLQRERELSqrdehvqELESYIDRLLVRIMETSPTLLQIP 648
Cdd:pfam09457   1 SRDELQDALQKQEEENR-------RLEDYIDNILLRIMEHNPSILEVP 41

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24308075  23 VTVLRARGLrgksSGAGSTSDAYTVIQVGR--EKYSTSVVEKThGCPEWREECSFELPPGAldgllraqeadagpapwaa 100
Cdd:cd08678   3 VKNIKANGL----SEAAGSSNPYCVLEMDEppQKYQSSTQKNT-SNPFWDEHFLFELSPNS------------------- 58

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24308075 101 ssaaaCELVLTTMHRSLIGVDKFLGQATVALDEVfgagRAQH--TQWYKLHSKPGKKEKERGEIevTIQFT 169
Cdd:cd08678  59 -----KELLFEVYDNGKKSDSKFLGLAIVPFDEL----RKNPsgRQIFPLQGRPYEGDSVSGSI--TVEFL 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 24308075  24 TVLRARGLRGKS-SGagsTSDAYTVIQVGREKYSTSVVEKThgC-PEWREECSFELPPGAlDGLLRAQEADAgpapwaas 101
Cdd:cd04025   5 HVLEARDLAPKDrNG---TSDPFVRVFYNGQTLETSVVKKS--CyPRWNEVFEFELMEGA-DSPLSVEVWDW-------- 70

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24308075 102 saaacelvlttmhrSLIGVDKFLGQATVALDEVFGAGraQHTQWYKLHSKPGKKEKERGEI 162
Cdd:cd04025  71 --------------DLVSKNDFLGKVVFSIQTLQQAK--QEEGWFRLLPDPRAEEESGGNL 115

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 24308075  21 VQVTVLRARGLRGKSSGAgsTSDAYTVIQVGREKYSTSVVEKTHGcPEWREECSFE 76
Cdd:cd04027   3 ISITVVCAQGLIAKDKTG--TSDPYVTVQVGKTKKRTKTIPQNLN-PVWNEKFHFE 55

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24308075  18 PTHVQVTVLRARGLRGKSSGAGSTSDAYTVIQV------GREKYSTSVVEKTHGCPEWREECSFEL 77
Cdd:cd00275   1 PLTLTIKIISGQQLPKPKGDKGSIVDPYVEVEIhglpadDSAKFKTKVVKNNGFNPVWNETFEFDV 66

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
                ....*....|....*....|....*....|....*....|....*....
gi 24308075  21 VQVTVLRARGLrgKSSGAGSTSDAYTVIQVGREKYSTSVVEKTHGcPEW 69
Cdd:cd04046   5 TQVHVHSAEGL--SKQDSGGGADPYVIIKCEGESVRSPVQKDTLS-PEF 50