C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 receptor (IL-1R) signaling pathway. Tollip is proposed to link serine/threonine kinase IRAK to IL-1Rs as well as inhibiting phosphorylation of IRAK. There is a single C2 domain present in Tollip. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972781729  12 AKLAKNYGMTRMDPYCRLRLGYAVYETPTAHNGAKNPRWNKVIHCTVPPGVDSFYLEIFDERAFSMDDRIAWTHITIPES 91
Cdd:cd04016   11 AKLVKNYGLTRMDPYCRIRVGHAVYETPTAYNGAKNPRWNKTIQCTLPEGVDSIYIEIFDERAFTMDERIAWTHITIPES 90

                         90       100       110
                 ....*....|....*....|....*....|.
gi 972781729  92 LRQGKVEDKWYSLSGRQGDDKEGMINLVMSY 122
Cdd:cd04016   91 VFNGETLDDWYSLSGKQGEDKEGMINLVFSY 121

C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 receptor (IL-1R) signaling pathway. Tollip is proposed to link serine/threonine kinase IRAK to IL-1Rs as well as inhibiting phosphorylation of IRAK. There is a single C2 domain present in Tollip. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972781729  12 AKLAKNYGMTRMDPYCRLRLGYAVYETPTAHNGAKNPRWNKVIHCTVPPGVDSFYLEIFDERAFSMDDRIAWTHITIPES 91
Cdd:cd04016   11 AKLVKNYGLTRMDPYCRIRVGHAVYETPTAYNGAKNPRWNKTIQCTLPEGVDSIYIEIFDERAFTMDERIAWTHITIPES 90

                         90       100       110
                 ....*....|....*....|....*....|.
gi 972781729  92 LRQGKVEDKWYSLSGRQGDDKEGMINLVMSY 122
Cdd:cd04016   91 VFNGETLDDWYSLSGKQGEDKEGMINLVFSY 121

Domain that may be involved in binding ubiquitin-conjugating enzymes (UBCs); CUE domains also occur in two protein of the IL-1 signal transduction pathway, tollip and TAB2. Ponting (Biochem. J.) "Proteins of the Endoplasmic reticulum" (in press)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 972781729   181 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 220
Cdd:smart00546   3 DEALHDLKEMFPNLDEEVIEAVLEANTGNVEATINNLLEG 42

CUE domain; CUE domains have been shown to bind ubiquitin. It has been suggested that CUE domains are related to pfam00627 and this has been confirmed by the structure of the domain. CUE domains also occur in two protein of the IL-1 signal transduction pathway, tollip and TAB2.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 972781729  181 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 220
Cdd:pfam02845   2 EQMLETLKEMFPDLDEEVIRAVLEASNGNVEAAINALLEG 41

C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 receptor (IL-1R) signaling pathway. Tollip is proposed to link serine/threonine kinase IRAK to IL-1Rs as well as inhibiting phosphorylation of IRAK. There is a single C2 domain present in Tollip. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972781729  12 AKLAKNYGMTRMDPYCRLRLGYAVYETPTAHNGAKNPRWNKVIHCTVPPGVDSFYLEIFDERAFSMDDRIAWTHITIPES 91
Cdd:cd04016   11 AKLVKNYGLTRMDPYCRIRVGHAVYETPTAYNGAKNPRWNKTIQCTLPEGVDSIYIEIFDERAFTMDERIAWTHITIPES 90

                         90       100       110
                 ....*....|....*....|....*....|.
gi 972781729  92 LRQGKVEDKWYSLSGRQGDDKEGMINLVMSY 122
Cdd:cd04016   91 VFNGETLDDWYSLSGKQGEDKEGMINLVFSY 121

Domain that may be involved in binding ubiquitin-conjugating enzymes (UBCs); CUE domains also occur in two protein of the IL-1 signal transduction pathway, tollip and TAB2. Ponting (Biochem. J.) "Proteins of the Endoplasmic reticulum" (in press)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 972781729   181 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 220
Cdd:smart00546   3 DEALHDLKEMFPNLDEEVIEAVLEANTGNVEATINNLLEG 42

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 972781729  14 LAKNYGMTRMDPYCRLRLGYA-VYETPTAHNGaKNPRWNKVIHCTV-PPGVDSFYLEIFDERAFSMDDRIAWTHITIPES 91
Cdd:cd00030   11 LPAKDLNGKSDPYVKVSLGGKqKFKTKVVKNT-LNPVWNETFEFPVlDPESDTLTVEVWDKDRFSKDDFLGEVEIPLSEL 89

                         90
                 ....*....|...
gi 972781729  92 LRQGKVEDKWYSL 104
Cdd:cd00030   90 LDSGKEGELWLPL 102

CUE domain found in ubiquitin-binding CUE proteins; This family includes many coupling of ubiquitin conjugation to endoplasmic reticulum degradation (CUE) domain containing proteins that are characterized by an FP and a di-leucine-like sequence and bind to monoubiquitin with varying affinities. Some higher eukaryotic CUE domain proteins do not bind monoubiquitin efficiently, since they carry LP, rather than FP among CUE domains. CUE domains form three-helix bundle structures and are distantly related to the ubiquitin-associated (UBA) domains which are widely occurring ubiquitin-binding motifs found in a broad range of cellular proteins in species ranging from yeast to human. The majority of family members contain one CUE domain, but some family members from fungi harbor two CUE domains.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 972781729 181 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLL 218
Cdd:cd14279    1 DEKLEQLQEMFPDLDEEVLEDVLEANNGDVEAAIDALL 38

CUE domain found in vacuolar protein sorting-associated protein 9 (VPS9) and similar proteins; VPS9, also called vacuolar protein-targeting protein 9, is a cytosolic yeast protein required for localization of vacuolar proteins, such as the soluble vacuolar hydrolases CPY and PrA. It may bind and act as an effector of a rab GTPase and plays a role in vacuolar protein sorting (VPS) pathway. VPS9 contains a region called GBH domain that is related to mammalian Ras-binding proteins, Rin1 and JC265, and may negatively regulate Ras-mediated signaling in yeast Saccharomyces cerevisiae. This model corresponds to the N-terminal CUE domain that interacts specifically with monoubiquitin and regulates intramolecular monoubiquitylation.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 972781729 181 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 220
Cdd:cd14369    3 KETLNTLQEMFPDLDKEIIKDVVIAKKGRIGECVDACLQL 42

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972781729  15 AKNYGMTRM-----DPYCRLRLGYAVYETPTAHNGAkNPRWNKVIHCTVP--PGVdSFYLEIFDERAFSmDDRIAWTHIT 87
Cdd:cd08391   15 AKDKFVGGLvkgksDPYVIVRVGAQTFKSKVIKENL-NPKWNEVYEAVVDevPGQ-ELEIELFDEDPDK-DDFLGRLSID 91

                         90       100       110
                 ....*....|....*....|....*....|....
gi 972781729  88 IPESLRQGKVeDKWYSLSgrqgDDKEGMINLVMS 121
Cdd:cd08391   92 LGSVEKKGFI-DEWLPLE----DVKSGRLHLKLE 120

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 972781729  21 TRMDPYCRLRL-GYAVYETPTAHNGAKNPRWNKVIHCTVPPGVDSF-----YLEIFDERAFSMDDRIAWTHITIPESLRQ 94
Cdd:cd04051   19 GKMKVYAVVWIdPSHKQSTPVDRDGGTNPTWNETLRFPLDERLLQQgrlalTIEVYCERPSLGDKLIGEVRVPLKDLLDG 98

                         90       100
                 ....*....|....*....|....*...
gi 972781729  95 GKVEDK----WYSLSGRQGDDKeGMINL 118
Cdd:cd04051   99 ASPAGElrflSYQLRRPSGKPQ-GVLNF 125

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 972781729  24 DPYCRLRLGYAVYETPTAHNGAkNPRWNkvIHCTVP---PGVDSFYLEIFDERAFSMDDRIAWTHITIPESLRQGKVE-- 98
Cdd:cd04024   25 DPYAILSVGAQRFKTQTIPNTL-NPKWN--YWCEFPifsAQNQLLKLILWDKDRFAGKDYLGEFDIALEEVFADGKTGqs 101

                         90       100
                 ....*....|....*....|....*.
gi 972781729  99 DKWYSL-SGRQGDD--KEGMINLVMS 121
Cdd:cd04024  102 DKWITLkSTRPGKTsvVSGEIHLQFS 127

CUE domain found in yeast ubiquitin-binding protein CUE5 (Cue5p), donuts protein 1 (DON1p) and similar proteins; Cue5p, also called coupling of ubiquitin conjugation to ER degradation protein 5, is encoded by the open reading frame (ORF) Yor042. It contains a CUE domain which exhibits weak ubiquitin binding properties. Donuts protein 1 (DON1p) is encoded by the ORF YDR273w. It localizes specifically to the prospore membrane and is expressed exclusively during meiosis. DON1p may function as a unique marker to investigate the defects associated with the impaired function of the meiotic plaque in the mpc- mutants.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 972781729 181 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 220
Cdd:cd14372    3 ESAIKILKEAFPDVDDKVIKAILIASQGDLEPAFNALLGL 42

UBA domain-like superfamily; The ubiquitin-associated (UBA) domain-like superfamily contains alpha-helical structural homology ubiquitin-binding domains, including UBA domains and coupling of ubiquitin conjugation to endoplasmic reticulum degradation (CUE) domains which share a common three-helical bundle architecture. UBA domains are commonly occurring sequence motifs found in proteins involved in ubiquitin-mediated proteolysis. They contribute to ubiquitin (Ub) binding or ubiquitin-like (UbL) domain binding. However, some kinds of UBA domains can only bind the UbL domain, but not the Ub domain. UBA domains are normally comprised of compact three-helix bundles which contain a conserved GF/Y-loop. They can bind polyubiquitin with high affinity. They also bind monoubiquitin and other proteins. Most UBA domain-containing proteins have one UBA domain, but some harbor two or three UBA domains. CUE domain containing proteins are characterized by an FP and a di-leucine-like sequence and bind to monoubiquitin with varying affinities. Some higher eukaryotic CUE domain proteins do not bind monoubiquitin efficiently, since they carry LP, rather than FP among CUE domains. This superfamily also includes many UBA-like domains found in AMP-activated protein kinase (AMPK) related kinases, the NXF family of mRNA nuclear export factors, elongation factor Ts (EF-Ts), nascent polypeptide-associated complex subunit alpha (NACA) and similar proteins. Although many UBA-like domains may have a conserved TG but not GF/Y-loop, they still show a high level of structural and sequence similarity with three-helical ubiquitin binding domains.

                         10        20
                 ....*....|....*....|....*....
gi 972781729 187 IQDMFPNmDQEVIRSVLEAQRGNKDAAIN 215
Cdd:cd00194    1 LVDITGA-SQEEAQQALEACGGNLNIAAN 28

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, 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. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. 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 972781729  25 PYCRLRLGYA-VYETPTAHngAKNPRWNK-VIHCTVPPGVDSFYLEIFDERAFSMDDRIAwtHITIP-ESLRQGKVEDKW 101
Cdd:cd08400   24 PYCVISLNEVkVARTKVRE--GPNPVWSEeFVFDDLPPDVNSFTISLSNKAKRSKDSEIA--EVTVQlSKLQNGQETDEW 99

                 ....*
gi 972781729 102 YSLSG 106
Cdd:cd08400  100 YPLSS 104

CUE domain found in NEDD4-binding protein 2 (N4BP2) and similar proteins; N4BP2 has been identified as an oncogene bcl-3 coding protein BCL-3-binding protein (B3BP) that participates in connecting transcriptional activation and genetic recombination of the Ig gene. In addition to BCL-3, it also interacts with p300/CBP histone acetyltransferases. N4BP2 shows intrinsic ATP binding and hydrolyzing activity. It contains an N-terminal ATP-binding region that is responsible for the interaction with BCL-3 and p300/CBP. N4BP2 also functions as a 5'-polynucleotide kinase that can transfer a phosphate group to the 5' end of DNA and RNA substrates. Moreover, N4BP2 contains a C-terminal MutS-related domain that possesses nicking endonuclease activity and may play a role in DNA mismatch repair (MMR). This model corresponds to CUE domain in the N-terminus of N4BP2.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 972781729 181 EEDLKAIQDMFP-NMDQEVIRSVLEAQRGNKDAAINSLLQM 220
Cdd:cd14365    2 EELFQQLQEMFSgKLDPSVVYMVLSECDFKVDNAMDTLLNL 42

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 972781729  24 DPYCRLRLGYAVYETPTAHNGAkNPRWNKVIHCTVPPGVDSFYLEIFDERAFSMDD 79
Cdd:cd04038   23 DPYVVLTLGNQKVKTRVIKKNL-NPVWNEELTLSVPNPMAPLKLEVFDKDTFSKDD 77

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 972781729  24 DPYCRLRLGYAVYETPTAHNGAkNPRWNKV-------IHctvppgvDSFYLEIFDE---RAFSMDDRIAwthitIP-ESL 92
Cdd:cd08377   23 DPFCVLELVNARLQTHTIYKTL-NPEWNKIftfpikdIH-------DVLEVTVYDEdkdKKPEFLGKVA-----IPlLSI 89

                         90       100       110
                 ....*....|....*....|....*....|.
gi 972781729  93 RQGkvEDKWYSLSGRQGDDK-EGMINLVMSY 122
Cdd:cd08377   90 KNG--ERKWYALKDKKLRTRaKGSILLEMDV 118

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 972781729  24 DPYCRL---RLGYAVYETPTAHNgAKNPRWNK--VIhCTVPPGVDS---FYLEIFDERAFSMDDRIAWTHITIPESLRQ- 94
Cdd:cd04041   24 DPYVTAsfaKFGKPLYSTRIIRK-DLNPVWEEtwFV-LVTPDEVKAgerLSCRLWDSDRFTADDRLGRVEIDLKELIEDr 101

                         90
                 ....*....|
gi 972781729  95 GKVEDKWYSL 104
Cdd:cd04041  102 NWMGRREDGF 111