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 2038168652   4 MGRLSITVVQAKLAKNYGMTRMDPYCRIRLGYAVYETPTAHNGAKNPRWNKVIQCTIPPGVDSFYIEIFDERAFSMDDRI 83
Cdd:cd04016     1 VGRLSITVVQAKLVKNYGLTRMDPYCRIRVGHAVYETPTAYNGAKNPRWNKTIQCTLPEGVDSIYIEIFDERAFTMDERI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2038168652  84 AWTHITIPETLKEGKHVDEWFSLSGKQGDDKEGMINLVMSY 124
Cdd:cd04016    81 AWTHITIPESVFNGETLDDWYSLSGKQGEDKEGMINLVFSY 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 2038168652   4 MGRLSITVVQAKLAKNYGMTRMDPYCRIRLGYAVYETPTAHNGAKNPRWNKVIQCTIPPGVDSFYIEIFDERAFSMDDRI 83
Cdd:cd04016     1 VGRLSITVVQAKLVKNYGLTRMDPYCRIRVGHAVYETPTAYNGAKNPRWNKTIQCTLPEGVDSIYIEIFDERAFTMDERI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2038168652  84 AWTHITIPETLKEGKHVDEWFSLSGKQGDDKEGMINLVMSY 124
Cdd:cd04016    81 AWTHITIPESVFNGETLDDWYSLSGKQGEDKEGMINLVFSY 121

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038168652   5 GRLSITVVQAK-LAKNYGMTRMDPYCRIRL--GYAVYETPTAHNGAkNPRWNKVIQCTIPPGVDSF-YIEIFDERAFSMD 80
Cdd:pfam00168   1 GRLTVTVIEAKnLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTL-NPVWNETFTFSVPDPENAVlEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*.
gi 2038168652  81 DRIAWTHITIpETLKEGKHVDEWFSL 106
Cdd:pfam00168  80 DFIGEVRIPL-SELDSGEGLDGWYPL 104

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 2038168652 177 REEDIQSIKDMFPTMDPEVIRSVLEAQGGNRDAAVNSLLQM 217
Cdd:pfam02845   1 NEQMLETLKEMFPDLDEEVIRAVLEASNGNVEAAINALLEG 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 2038168652   4 MGRLSITVVQAKLAKNYGMTRMDPYCRIRLGYAVYETPTAHNGAKNPRWNKVIQCTIPPGVDSFYIEIFDERAFSMDDRI 83
Cdd:cd04016     1 VGRLSITVVQAKLVKNYGLTRMDPYCRIRVGHAVYETPTAYNGAKNPRWNKTIQCTLPEGVDSIYIEIFDERAFTMDERI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2038168652  84 AWTHITIPETLKEGKHVDEWFSLSGKQGDDKEGMINLVMSY 124
Cdd:cd04016    81 AWTHITIPESVFNGETLDDWYSLSGKQGEDKEGMINLVFSY 121

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038168652   5 GRLSITVVQAK-LAKNYGMTRMDPYCRIRL--GYAVYETPTAHNGAkNPRWNKVIQCTIPPGVDSF-YIEIFDERAFSMD 80
Cdd:pfam00168   1 GRLTVTVIEAKnLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTL-NPVWNETFTFSVPDPENAVlEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*.
gi 2038168652  81 DRIAWTHITIpETLKEGKHVDEWFSL 106
Cdd:pfam00168  80 DFIGEVRIPL-SELDSGEGLDGWYPL 104

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 2038168652   5 GRLSITVVQAK-LAKNYGMTRMDPYCRIRLGYAVYETPTAHNGAKNPRWNKVIQCTIPP-GVDSFYIEIFDERaFSMDDR 82
Cdd:cd08681     1 GTLVVVVLKARnLPNKRKLDKQDPYCVLRIGGVTKKTKTDFRGGQHPEWDEELRFEITEdKKPILKVAVFDDD-KRKPDL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2038168652  83 IAWTHITIPETLKEGKHvDEWFSLsgKQGDDKEGMINLVMSY 124
Cdd:cd08681    80 IGDTEVDLSPALKEGEF-DDWYEL--TLKGRYAGEVYLELTF 118

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 2038168652  177 REEDIQSIKDMFPTMDPEVIRSVLEAQGGNRDAAVNSLLQM 217
Cdd:smart00546   2 NDEALHDLKEMFPNLDEEVIEAVLEANTGNVEATINNLLEG 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 2038168652   5 GRLSITVVQAK--LAKNYGMTRM-----DPYCRIRLGYAVYETPTAHNGAkNPRWNKVIQCTIP--PGVdSFYIEIFDER 75
Cdd:cd08391     1 GVLRIHVIEAQdlVAKDKFVGGLvkgksDPYVIVRVGAQTFKSKVIKENL-NPKWNEVYEAVVDevPGQ-ELEIELFDED 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2038168652  76 AFSmDDRIAWTHITIPETLKEGKhVDEWFSLSgkqgDDKEGMINLVMS 123
Cdd:cd08391    79 PDK-DDFLGRLSIDLGSVEKKGF-IDEWLPLE----DVKSGRLHLKLE 120

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 2038168652    6 RLSITVVQAK-LAKNYGMTRMDPYCRIRLGYA---VYETPTAHNGAkNPRWNKVIQCTI-PPGVDSFYIEIFDERAFSMD 80
Cdd:smart00239   1 TLTVKIISARnLPPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTL-NPVWNETFEFEVpPPELAELEIEVYDKDRFGRD 79

                           90       100
                   ....*....|....*....|...
gi 2038168652   81 DRIAWTHITIpETLKEGKHVDEW 103
Cdd:smart00239  80 DFIGQVTIPL-SDLLLGGRHEKL 101

CUE domain found in CUE domain-containing protein 1 (CUED1) and similar proteins; The subfamily includes a group of uncharacterized CUE domain-containing protein termed CUED1. Their biological function remains unknown.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2038168652 178 EEDIQSIKDMFPTMDPEVIRSVLEAQGGNRDAAVNSLLQM 217
Cdd:cd14366     3 EQAMEDLKTMFPNMDREVIEAVLRANNGHVEATIDQLLAM 42

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 2038168652   6 RLSITVVQAK-LAKNYGMTRMDPYCRIRLGYAVYETPTAHNgAKNPRWNKVIQCTIPPGVDS-FYIEIFDERAFSMDDRI 83
Cdd:cd04025     1 RLRCHVLEARdLAPKDRNGTSDPFVRVFYNGQTLETSVVKK-SCYPRWNEVFEFELMEGADSpLSVEVWDWDLVSKNDFL 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2038168652  84 AWTHITIpETLKEGKHVDEWFSLS--GKQGDDKEG 116
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 2038168652   7 LSITVVQA-----KLAKNygmtrmdPYCRIRLGYA-VYETPTAHngAKNPRWNK-VIQCTIPPGVDSFYIEIFDERAFSM 79
Cdd:cd08400     6 LQLNVLEAhklpvKHVPH-------PYCVISLNEVkVARTKVRE--GPNPVWSEeFVFDDLPPDVNSFTISLSNKAKRSK 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2038168652  80 DDRIAwtHITIP-ETLKEGKHVDEWFSLSGKQGDDKE--GMINLVMSYTS 126
Cdd:cd08400    77 DSEIA--EVTVQlSKLQNGQETDEWYPLSSASPLKGGewGSLRIRARYSH 124

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 2038168652 177 REEDIQSIKDMFP-TMDPEVIRSVLEAQGGNRDAAVNSLLQM 217
Cdd:cd14365     1 QEELFQQLQEMFSgKLDPSVVYMVLSECDFKVDNAMDTLLNL 42

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 2038168652   5 GRLSITVVQAK-LAKN--YGMTRMDPYCRIRLGYAVYETPTAHNGAkNPRWNkvIQCTIP---PGVDSFYIEIFDERAFS 78
Cdd:cd04024     1 GVLRVHVVEAKdLAAKdrSGKGKSDPYAILSVGAQRFKTQTIPNTL-NPKWN--YWCEFPifsAQNQLLKLILWDKDRFA 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2038168652  79 MDDRIAWTHITIPETLKEGK--HVDEWFSL---SGKQGDDKEGMINLVMS 123
Cdd:cd04024    78 GKDYLGEFDIALEEVFADGKtgQSDKWITLkstRPGKTSVVSGEIHLQFS 127

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 2038168652   5 GRLSITVVQAK-LAKNYGMTRMDPYCRIRLGYAVYETPTAHNGAKNPRWNKVIQCTIP-PGVDSFY---IEIFDERAFSM 79
Cdd:cd04049     1 GTLEVLLISAKgLQDTDFLGKIDPYVIIQCRTQERKSKVAKGDGRNPEWNEKFKFTVEyPGWGGDTkliLRIMDKDNFSD 80

                          90
                  ....*....|....*...
gi 2038168652  80 DDRIAWTHITIPETLKEG 97
Cdd:cd04049    81 DDFIGEATIHLKGLFEEG 98

CUE2 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 second CUE domain.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 2038168652 179 EDIQSIKDMFPTMDPEVIRSVLEAQGGNRDAAVNSLL 215
Cdd:cd14375     2 NDLDELKDMFPNLDSEVIEDCYVLCEKNVERTVSALL 38

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 2038168652  26 DPYCRIRL-GYAVYETPTAHNgAKNPRWNKVIQCTIPPGVDSFYIEIFDERAFSMDDRIAWTHITIPETLKEGKHVDEWF 104
Cdd:cd04054    22 DPYCIVKVdNEVIIRTATVWK-TLNPFWGEEYTVHLPPGFHTVSFYVLDEDTLSRDDVIGKVSLTREVISAHPRGIDGWM 100

                          90       100
                  ....*....|....*....|
gi 2038168652 105 SLSGKQGDDK-EGMINLVMS 123
Cdd:cd04054   101 NLTEVDPDEEvQGEIHLELS 120

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 2038168652 179 EDIQSIKDMFPTMDPEVIRSVLEAQGGNRDAAVNSLLQM 217
Cdd:cd14371     2 ADVELLSSMFPGVSADSIAEVYEANGGDLDLTIDMLTQL 40