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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15237921  34 LVFLTIAGSVIPKRVMESDSIASVKLRIQSIKGFFVKKQKLLYDGREVSRNDSqIRDYGLADGKLLHLVIRL 105
Cdd:cd01802   3 LFIETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYC-LHDYNITDGSTLKLVLAM 73

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15237921  34 LVFLTIAGSVIPKRVMESDSIASVKLRIQSIKGFFVKKQKLLYDGREVSRNDSqIRDYGLADGKLLHLVIRL 105
Cdd:cd01802   3 LFIETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYC-LHDYNITDGSTLKLVLAM 73

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15237921     38 TIAGSVIPKRVMESDSIASVKLRIQSIKGFFVKKQKLLYDGReVSRNDSQIRDYGLADGKLLHLVIR 104
Cdd:smart00213   7 TLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGK-VLEDDRTLADYGIQDGSTIHLVLR 72

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15237921   111 ISVRTVDGKEFELVVERSRNVGYVKQQIASKEkelGIPRDHE-LTLDGEELDDQRLITDLCQNGDNVIHLLISKS 184
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKE---GVPPEQQrLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 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 15237921    111 ISVRTVDGKEFELVVERSRNVGYVKQQIASKEkelGIPRD-HELTLDGEELDDQRLITDLCQNGDNVIHLLIS 182
Cdd:smart00213   3 LTVKTLDGKTITLEVKPSDTVSELKEKIAELT---GIPPEqQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15237921  34 LVFLTIAGSVIPKRVMESDSIASVKLRIQSIKGFFVKKQKLLYDGREVSRNDSqIRDYGLADGKLLHLVIRL 105
Cdd:cd01802   3 LFIETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYC-LHDYNITDGSTLKLVLAM 73

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15237921     38 TIAGSVIPKRVMESDSIASVKLRIQSIKGFFVKKQKLLYDGReVSRNDSQIRDYGLADGKLLHLVIR 104
Cdd:smart00213   7 TLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGK-VLEDDRTLADYGIQDGSTIHLVLR 72

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15237921  38 TIAGSVIPKRVMESDSIASVKLRIQSIKGFFVKKQKLLYDGREVsRNDSQIRDYGLADGKLLHLV 102
Cdd:cd17039   5 TLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKEL-KDDKTLSDYGIKDGSTIHLV 68

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15237921  38 TIAGSVIPKRVMESDSIASVKLRIQSIKGFFVKKQKLLYDGREVsRNDSQIRDYGLADGKLLHLVIRLSD 107
Cdd:COG5272   7 TLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQL-EDDRTLADYNIQKESTLHLVTRTLG 75

ubiquitin-like (Ubl) domain found in neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) and similar proteins; NEDD8, also termed Neddylin, or RELATED TO UBIQUITIN (RUB/Rub1p) in plant and yeast, is a ubiquitin-like protein that conjugates to nuclear proteins in a manner analogous to ubiquitination and sentrinization. It modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. NEDD8 deamidation and its inhibition of Cullin-RING ubiquitin ligases (CRLs) activity are responsible for Cycle-inhibiting factor (Cif)/Cif homolog in Burkholderia pseudomallei (CHBP)-induced cytopathic effect. NEDD8 contains a single conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. 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. Ubl NEDD8, contains many of the same lysines (K6, K11, K27, K33, K48) as Ub, where K27 has an role (other than conjugation) in the mechanism of protein neddylation.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15237921 111 ISVRTVDGKEFELVVERSRNVGYVKQQIASKEkelGIPRDHE-LTLDGEELDDQRLITDLCQNGDNVIHLLIS 182
Cdd:cd01806   1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKE---GIPPQQQrLIFSGKQMNDEKTAADYKIEGGSVLHLVLA 70

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15237921  38 TIAGSVIPKRVMESDSIASVKLRIQSIKGFFVKKQKLLYDGREVSRNDSqIRDYGLADGKLLHLVIRL 105
Cdd:cd01803   7 TLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRT-LSDYNIQKESTLHLVLRL 73

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15237921  48 VMESDSIASVKLRIQSIKGFFVKKQKLLYDGReVSRNDSQIRDYGLaDGKLLHLVIR 104
Cdd:cd01809  17 VPEEITVKEFKEHIASSVNIPAEKQRLIFQGR-VLQDDKKLKEYDV-DGKVIHLVER 71

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15237921  48 VMESDSIASVKLRIQSIKGFFVKKQKLLYDGREVSrNDSQIRDYGLADGKLLHLVIR 104
Cdd:cd01807  17 VSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLA-DEHSLSDYSIGPGSKIHLVVK 72