CUE domain found in the C-terminal of toll-interacting protein (Tollip) and similar proteins; Tollip is a new component of the IL-1RI pathway which contains an N-terminal C2 domain and a C-terminal CUE domain. Tollip binds to the cytoplasmic TIR domain of IL-1Rs after IL-1 stimulation. It is sufficient for recruitment of IRAK to IL-1Rs and negatively regulates IL-1-induced signaling by inhibiting IRAK phosphorylation. In addition, Tollip directly interacts with toll-like receptors TLR2 and TLR4, and plays an inhibitory role in TLR-mediated cell activation through suppressing phosphorylation and kinase activity of IRAK. Moreover, Tollip can associate with GAT domains of Tom1 and its related proteins Tom1L1 and Tom1L2, and facilitate the recruitment of clathrin onto endosomes.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 20140803 230 SEEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 270
Cdd:cd14363   1 TEEDLKQIQEMFPNVDKEVIKSVLEANRGNKDAAINSLLQM 41

CUE domain found in the C-terminal of toll-interacting protein (Tollip) and similar proteins; Tollip is a new component of the IL-1RI pathway which contains an N-terminal C2 domain and a C-terminal CUE domain. Tollip binds to the cytoplasmic TIR domain of IL-1Rs after IL-1 stimulation. It is sufficient for recruitment of IRAK to IL-1Rs and negatively regulates IL-1-induced signaling by inhibiting IRAK phosphorylation. In addition, Tollip directly interacts with toll-like receptors TLR2 and TLR4, and plays an inhibitory role in TLR-mediated cell activation through suppressing phosphorylation and kinase activity of IRAK. Moreover, Tollip can associate with GAT domains of Tom1 and its related proteins Tom1L1 and Tom1L2, and facilitate the recruitment of clathrin onto endosomes.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 20140803 230 SEEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 270
Cdd:cd14363   1 TEEDLKQIQEMFPNVDKEVIKSVLEANRGNKDAAINSLLQM 41

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 20140803    231 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 270
Cdd:smart00546   3 DEALHDLKEMFPNLDEEVIEAVLEANTGNVEATINNLLEG 42

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 20140803     54 RLNITVVQAK-LAKNYGMTRMDPYCRLRLGYA---VYETPTAHNGAkNPRWNKVIHCTV-PPGVDSFYLEIFDERAFSMD 128
Cdd:smart00239   1 TLTVKIISARnLPPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTL-NPVWNETFEFEVpPPELAELEIEVYDKDRFGRD 79

                           90       100
                   ....*....|....*....|...
gi 20140803    129 DRIAWTHITIpESLRQGKVEDKW 151
Cdd:smart00239  80 DFIGQVTIPL-SDLLLGGRHEKL 101

CUE domain found in the C-terminal of toll-interacting protein (Tollip) and similar proteins; Tollip is a new component of the IL-1RI pathway which contains an N-terminal C2 domain and a C-terminal CUE domain. Tollip binds to the cytoplasmic TIR domain of IL-1Rs after IL-1 stimulation. It is sufficient for recruitment of IRAK to IL-1Rs and negatively regulates IL-1-induced signaling by inhibiting IRAK phosphorylation. In addition, Tollip directly interacts with toll-like receptors TLR2 and TLR4, and plays an inhibitory role in TLR-mediated cell activation through suppressing phosphorylation and kinase activity of IRAK. Moreover, Tollip can associate with GAT domains of Tom1 and its related proteins Tom1L1 and Tom1L2, and facilitate the recruitment of clathrin onto endosomes.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 20140803 230 SEEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 270
Cdd:cd14363   1 TEEDLKQIQEMFPNVDKEVIKSVLEANRGNKDAAINSLLQM 41

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 20140803  55 LNITVVQAK-LAKNYGMTRMDPYCRLRLGYA-VYETPTAHNGaKNPRWNKVIHCTV-PPGVDSFYLEIFDERAFSMDDRI 131
Cdd:cd00030   1 LRVTVIEARnLPAKDLNGKSDPYVKVSLGGKqKFKTKVVKNT-LNPVWNETFEFPVlDPESDTLTVEVWDKDRFSKDDFL 79

                        90       100
                ....*....|....*....|...
gi 20140803 132 AWTHITIPESLRQGKVEDKWYSL 154
Cdd:cd00030  80 GEVEIPLSELLDSGKEGELWLPL 102

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 20140803   231 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 270
Cdd:pfam02845   2 EQMLETLKEMFPDLDEEVIRAVLEASNGNVEAAINALLEG 41

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 20140803  53 GRLNITVVQAK-LAKNYGMTRMDPYCRLRLGYAVYETPTAHNGAKNPRWNKVIHCTVPP-GVDSFYLEIFDERaFSMDDR 130
Cdd:cd08681   1 GTLVVVVLKARnLPNKRKLDKQDPYCVLRIGGVTKKTKTDFRGGQHPEWDEELRFEITEdKKPILKVAVFDDD-KRKPDL 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 20140803 131 IAWTHITIPESLRQGKVeDKWYSLSgrQGDDKEGMINLVMSY 172
Cdd:cd08681  80 IGDTEVDLSPALKEGEF-DDWYELT--LKGRYAGEVYLELTF 118

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 20140803  53 GRLNITVVQAK--LAKNYGMTRM-----DPYCRLRLGYAVYETPTAHNGAkNPRWNKVIHCTVP--PGVdSFYLEIFDER 123
Cdd:cd08391   1 GVLRIHVIEAQdlVAKDKFVGGLvkgksDPYVIVRVGAQTFKSKVIKENL-NPKWNEVYEAVVDevPGQ-ELEIELFDED 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 20140803 124 AFSmDDRIAWTHITIPESLRQGKVeDKWYSLSgrqgDDKEGMINLVMS 171
Cdd:cd08391  79 PDK-DDFLGRLSIDLGSVEKKGFI-DEWLPLE----DVKSGRLHLKLE 120

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 20140803  53 GRLNITVVQAK-LAKN--YGMTRMDPYCRLRLGYAVYETPTAHNGAkNPRWNkvIHCTVP---PGVDSFYLEIFDERAFS 126
Cdd:cd04024   1 GVLRVHVVEAKdLAAKdrSGKGKSDPYAILSVGAQRFKTQTIPNTL-NPKWN--YWCEFPifsAQNQLLKLILWDKDRFA 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 20140803 127 MDDRIAWTHITIPESLRQGKVE--DKWYSL-SGRQGDD--KEGMINLVMS 171
Cdd:cd04024  78 GKDYLGEFDIALEEVFADGKTGqsDKWITLkSTRPGKTsvVSGEIHLQFS 127

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 20140803  55 LNITVVQAK-LAKNYGMTRMDPYCRLRL-GYAVYETPTAHNGAKNPRWNKVIHCTVPPGVDSF-----YLEIFDERAFSM 127
Cdd:cd04051   2 LEITIISAEdLKNVNLFGKMKVYAVVWIdPSHKQSTPVDRDGGTNPTWNETLRFPLDERLLQQgrlalTIEVYCERPSLG 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 20140803 128 DDRIAWTHITIPESLRQGKVEDK----WYSLSGRQGDDKeGMINL 168
Cdd:cd04051  82 DKLIGEVRVPLKDLLDGASPAGElrflSYQLRRPSGKPQ-GVLNF 125

CUE domain found in yeast ubiquitin-binding protein CUE3 (Cue3p) and similar proteins; Cue3p, also called coupling of ubiquitin conjugation to ER degradation protein 3, is encoded by the open reading frame (ORF) YGL110C. It is involved in the intramolecular monoubiquitination that serves as a regulatory signal in a variety of cellular processes in yeast. Cue3p contains a CUE domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 20140803 231 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 270
Cdd:cd14373   1 EEDISTLSELFPDLTEYQIKTLLKKYDNNVELVTNILLEN 40

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 20140803  54 RLNITVVQAK-LAKNYGMTRMDPYCRLRLGYAVYETPTAHNgAKNPRWNKVIHCTVPPGVDS-FYLEIFDERAFSMDDRI 131
Cdd:cd04025   1 RLRCHVLEARdLAPKDRNGTSDPFVRVFYNGQTLETSVVKK-SCYPRWNEVFEFELMEGADSpLSVEVWDWDLVSKNDFL 79

                        90       100       110
                ....*....|....*....|....*....|....*
gi 20140803 132 AWTHITIpESLRQGKVEDKWYSLS--GRQGDDKEG 164
Cdd:cd04025  80 GKVVFSI-QTLQQAKQEEGWFRLLpdPRAEEESGG 113

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 20140803  55 LNITVVQA-----KLAKNygmtrmdPYCRLRLGYA-VYETPTAHngAKNPRWNK-VIHCTVPPGVDSFYLEIFDERAFSM 127
Cdd:cd08400   6 LQLNVLEAhklpvKHVPH-------PYCVISLNEVkVARTKVRE--GPNPVWSEeFVFDDLPPDVNSFTISLSNKAKRSK 76

                        90       100       110
                ....*....|....*....|....*....|
gi 20140803 128 DDRIAwtHITIP-ESLRQGKVEDKWYSLSG 156
Cdd:cd08400  77 DSEIA--EVTVQlSKLQNGQETDEWYPLSS 104

CUE domain found in CTC-interacting domain proteins CID5, CID6, CID7 and similar proteins; CID7 is encoded by ubiquitously expressed gene CID7. It contains an N-terminal PABC-interacting domain (PAM2 or PABP-interacting motif 2) which is also found in the human Paip1 and Paip2. At this point, it functions as an interaction partner of the PABC domain of Arabidopsis thaliana Poly(A)-binding proteins. It also harbors an ubiquitin-associated (UBA)-like CUE domain and a C-terminal small MutS-related (SMR) domain. CID5 and CID6 are encoded by gene CID5, CID6, respectively. CID5 is only expressed in immature siliques. The biological function of CID5 and CID6 remain unclear.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 20140803 232 EDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 270
Cdd:cd14371   2 ADVELLSSMFPGVSADSIAEVYEANGGDLDLTIDMLTQL 40

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 20140803 237 IQDMFPNmDQEVIRSVLEAQRGNKDAAIN 265
Cdd:cd00194   1 LVDITGA-SQEEAQQALEACGGNLNIAAN 28

CUE1 domain found in yeast ubiquitin-binding protein CUE2 (Cue2p) and similar proteins; Cue2p, also called coupling of ubiquitin conjugation to ER degradation protein 2, is encoded by the open reading frame (ORF) YKL090W. It is involved in the intramolecular monoubiquitination that serves as a regulatory signal in a variety of cellular processes in yeast. Cue2p contains two tandem CUE domains at the N-terminus. Both of them can bind monoubiquitin independently. This model corresponds to the first CUE domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 20140803 231 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLL 268
Cdd:cd14374   1 ESKISTLRDMFPNLSIDQAVDALKTNNNDLDQTIDYLL 38

CUE domain found in activating signal cointegrator 1 complex subunit 2 (ASCC2) and similar proteins; ASCC2, also called ASC-1 complex subunit p100 or Trip4 complex subunit p100, together with ASCC1 (also called p50) and ASCC3 (also called p300), form the activating signal cointegrator complex (ASCC). ASCC plays an essential role in activating protein 1 (AP-1), serum response factor (SRF), and nuclear factor kappaB (NF-kappaB) transactivation. It acts as a transcriptional coactivator of nuclear receptors and regulates the transrepression between nuclear receptors and either AP-1 or NF-kappaB in vivo. Members in this family all contain a CUE domain.

                        10        20        30
                ....*....|....*....|....*....|..
gi 20140803 237 IQDMFPNMDQEVIRSVLEAQRGNKDAAINSLL 268
Cdd:cd14364   7 VKDILPDLGEGFIEACLEHYNGNVERVINALL 38

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20140803  54 RLNITVVQAKLAKNYG-MTRMDPYCRLRLgyavyetPTAHNGAK---------NPRWNKVIHCTVPPGVDSFyLEI--FD 121
Cdd:cd04036   1 LLTVRVLRATNITKGDlLSTPDCYVELWL-------PTASDEKKrtktiknsiNPVWNETFEFRIQSQVKNV-LELtvMD 72

                ....*...
gi 20140803 122 ERAFsMDD 129
Cdd:cd04036  73 EDYV-MDD 79