first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2071360585  53 MHIFLRSQNLHTVDI-ENGTVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDLEINSC-LADGATVDVSVRLRGG 124
Cdd:cd01793     1 MQLFVRAQSLHTLEVsGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCgIPDLATLEVAVRLLGG 74

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2071360585  53 MHIFLRSQNLHTVDI-ENGTVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDLEINSC-LADGATVDVSVRLRGG 124
Cdd:cd01793     1 MQLFVRAQSLHTLEVsGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCgIPDLATLEVAVRLLGG 74

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2071360585  55 IFLRSQ--NLHTVDIENG-TVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDLEINSC-LADGATVDVSVRLR 122
Cdd:pfam00240   1 ITVKTLdgKKITLEVDPTdTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYgIEDGSTIHLVLRQR 72

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2071360585   53 MHIFLRSQN--LHTVDIENG-TVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDLEINSC-LADGATVDVSVR 120
Cdd:smart00213   1 IELTVKTLDgkTITLEVKPSdTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYgIQDGSTIHLVLR 72

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2071360585  53 MHIFLRSQNLHTVDI-ENGTVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDLEINSC-LADGATVDVSVRLRGG 124
Cdd:cd01793     1 MQLFVRAQSLHTLEVsGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCgIPDLATLEVAVRLLGG 74

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2071360585  55 IFLRSQ--NLHTVDIENG-TVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDLEINSC-LADGATVDVSVRLR 122
Cdd:pfam00240   1 ITVKTLdgKKITLEVDPTdTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYgIEDGSTIHLVLRQR 72

30S ribosomal protein S30e; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 2071360585 127 HGSLARAGKVKGQTPKVEKQEkRKKKTGRAKRRMQFNKRFVNV 169
Cdd:PRK09336    4 HGSLTKAGKVRSQTPKIPPKP-KKNEVPRVRNRREYERRVLKA 45

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2071360585  54 HIFLRSQNLHTVDIE-NGTVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDLEINSC-LADGATVDV 117
Cdd:cd17039     2 TVKTLDGKTYTVEVDpDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYgIKDGSTIHL 67

ubiquitin; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2071360585  71 TVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDLEINSC-LADGATVDVSVRLRGG 124
Cdd:PTZ00044   22 TVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYkVVPGSTIHMVLQLRGG 76

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2071360585  55 IFLRSQNLHTVDIE---NGTVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDLEINSC-LADGATVDVsVRLR 122
Cdd:cd01798     1 VFVRFNSSHGFPVEvdsDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCdLGQQSIVHA-VQGP 71

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2071360585  53 MHIFLRSQNLHTVDIE---NGTVYSLKKFLEKEEGLCAEEQILYYAGNPLEDdleiNSCLAD-----GATVDVSVRLRGG 124
Cdd:cd01803     1 MQIFVKTLTGKTITLEvepSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLED----GRTLSDyniqkESTLHLVLRLRGG 76

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2071360585  53 MHIFLRSQN--LHTVDIE-NGTVYSLKKFLEKEEGLCAEEQILYYAGNPLEDDL---EINscLADGATVDVSVRLR 122
Cdd:cd01810     1 LSIFVRNEKgqSHTYEVRlTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLplgEYG--LKPQSTIHMNLRLR 74