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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 972781798  61 QRAFSMDDRIAWTHITIPESLRQGKVEDKWYSLSGRQGDDKEGMINLVMSY 111
Cdd:cd04016   71 ERAFTMDERIAWTHITIPESVFNGETLDDWYSLSGKQGEDKEGMINLVFSY 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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 972781798  61 QRAFSMDDRIAWTHITIPESLRQGKVEDKWYSLSGRQGDDKEGMINLVMSY 111
Cdd:cd04016   71 ERAFTMDERIAWTHITIPESVFNGETLDDWYSLSGKQGEDKEGMINLVFSY 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 972781798   170 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 209
Cdd:smart00546   3 DEALHDLKEMFPNLDEEVIEAVLEANTGNVEATINNLLEG 42

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 972781798  61 QRAFSMDDRIAWTHITIPESLRQGKVEDKWYSLSGRQGDDKEGMINLVMSY 111
Cdd:cd04016   71 ERAFTMDERIAWTHITIPESVFNGETLDDWYSLSGKQGEDKEGMINLVFSY 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 972781798   170 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 209
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 972781798  170 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 209
Cdd:pfam02845   2 EQMLETLKEMFPDLDEEVIRAVLEASNGNVEAAINALLEG 41

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
                 ....*....|....*....|....*....|....*....
gi 972781798 171 EDLKAiqdMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 209
Cdd:cd14366    7 EDLKT---MFPNMDREVIEAVLRANNGHVEATIDQLLAM 42

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 972781798 170 EEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 209
Cdd:cd14373    1 EEDISTLSELFPDLTEYQIKTLLKKYDNNVELVTNILLEN 40

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 972781798 171 EDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQM 209
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 972781798 176 IQDMFPNmDQEVIRSVLEAQRGNKDAAIN 204
Cdd:cd00194    1 LVDITGA-SQEEAQQALEACGGNLNIAAN 28

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 972781798 176 IQDMFPNMDQEVIRSVLEAQRGNKDAAINSLL 207
Cdd:cd14364    7 VKDILPDLGEGFIEACLEHYNGNVERVINALL 38