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 568988119    4 RWVRVTVLRGCVGCRTVAVPATATGRDLKERIFAETSFPVAEQRLWRGDREIPDWIKIG-DLTSKTCHLFVNL 75
Cdd:cd17049     1 RLPRVTVLHEYIGCRTFEVPPSAAVRDIKELIYEETDFPVSEQQLWHNGKELSDWVKIGgLVPSGSHEIFLTL 73

DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, an important chaperonine family. Hsp40 proteins are characterized by the presence of a J domain, which mediates the interaction with Hsp70. They may contain other domains as well, and the architectures provide a means of classification.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 568988119  4331 ESERKKIIRRLYLKWHPDKNPENHDiANEVFKHLQN 4366
Cdd:pfam00226   14 DEEIKKAYRKLALKYHPDKNPGDPE-AEEKFKEINE 48

ubiquitin-like (Ubl) domain found in Sacsin and similar proteins; Sacsin, also termed DnaJ homolog subfamily C member 29 (DNAJC29), is encoded by SACS gene that is highly expressed in the brain. Mutations in SACS can cause the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) which is characterized by early-onset spastic ataxia. Sacsin is a modular protein that is localized on the mitochondrial surface and possibaly required for normal mitochondrial network organization. Sacsin knockdown resulted in a reduction in cells expressing plyglutamine-expanded ataxin-1, which correlated with a loss of cells with large nuclear ataxin-1 incusions. At the N-terminus, sacsin contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which can interact with the proteasome. At the C-terminus, sacsin harbors a protein-protein interaction J-domain followed by an higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain. The J-domain is typically associated with DnaJ-like co-chaperones involved in regulation of the Hsp70 heat shock system.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568988119    4 RWVRVTVLRGCVGCRTVAVPATATGRDLKERIFAETSFPVAEQRLWRGDREIPDWIKIG-DLTSKTCHLFVNL 75
Cdd:cd17049     1 RLPRVTVLHEYIGCRTFEVPPSAAVRDIKELIYEETDFPVSEQQLWHNGKELSDWVKIGgLVPSGSHEIFLTL 73

HEPN domain protein, predicted toxin of MNT-HEPN system [Defense mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988119 4460 LRQARANFSAARNDLHKNANEWVCFKCYLSTKLALIAADYAVRGKSDK--DVkpTALAQKIEEYSQQLEGLTNDVHTLEA 4537
Cdd:COG2250     1 LRRAERDLEAAELLLEEGRYDLACFHAQQAAEKALKALLLALGGEPPKthDL--RELLELLEKLLPEPEELRDLLRLLDK 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 568988119 4538 YGVDSlktRYPDLLPfpqIPNDRFTSEVAMRVMECTACIIIKLENFIQQ 4586
Cdd:COG2250    79 AYIPA---RYPDALP---EGPEEYTREEAEEALELAEEVLEFVEKLLKE 121

DnaJ domain; DnaJ domains (J-domains) are associated with hsp70 heat-shock system and it is thought that this domain mediates the interaction. DnaJ-domain is therefore part of a chaperone (protein folding) system. The T-antigens, although not in Prosite are confirmed as DnaJ containing domains from literature.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 568988119  4331 ESERKKIIRRLYLKWHPDKNPENHDiANEVFKHLQN 4366
Cdd:pfam00226   14 DEEIKKAYRKLALKYHPDKNPGDPE-AEEKFKEINE 48

chaperone protein DnaJ; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568988119 4318 EVTSVVEQAWKlpeSERKKIIRRLYLKWHPDKNPENHDI------ANEVFKHLQNEinrlEKQAFLDQ 4379
Cdd:PRK14281    7 EVLGVSRSADK---DEIKKAYRKLALKYHPDKNPDNKEAeehfkeVNEAYEVLSND----DKRRRYDQ 67

ubiquitin-like (Ubl) domain found in Sacsin and similar proteins; Sacsin, also termed DnaJ homolog subfamily C member 29 (DNAJC29), is encoded by SACS gene that is highly expressed in the brain. Mutations in SACS can cause the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) which is characterized by early-onset spastic ataxia. Sacsin is a modular protein that is localized on the mitochondrial surface and possibaly required for normal mitochondrial network organization. Sacsin knockdown resulted in a reduction in cells expressing plyglutamine-expanded ataxin-1, which correlated with a loss of cells with large nuclear ataxin-1 incusions. At the N-terminus, sacsin contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which can interact with the proteasome. At the C-terminus, sacsin harbors a protein-protein interaction J-domain followed by an higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain. The J-domain is typically associated with DnaJ-like co-chaperones involved in regulation of the Hsp70 heat shock system.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568988119    4 RWVRVTVLRGCVGCRTVAVPATATGRDLKERIFAETSFPVAEQRLWRGDREIPDWIKIG-DLTSKTCHLFVNL 75
Cdd:cd17049     1 RLPRVTVLHEYIGCRTFEVPPSAAVRDIKELIYEETDFPVSEQQLWHNGKELSDWVKIGgLVPSGSHEIFLTL 73

HEPN domain protein, predicted toxin of MNT-HEPN system [Defense mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568988119 4460 LRQARANFSAARNDLHKNANEWVCFKCYLSTKLALIAADYAVRGKSDK--DVkpTALAQKIEEYSQQLEGLTNDVHTLEA 4537
Cdd:COG2250     1 LRRAERDLEAAELLLEEGRYDLACFHAQQAAEKALKALLLALGGEPPKthDL--RELLELLEKLLPEPEELRDLLRLLDK 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 568988119 4538 YGVDSlktRYPDLLPfpqIPNDRFTSEVAMRVMECTACIIIKLENFIQQ 4586
Cdd:COG2250    79 AYIPA---RYPDALP---EGPEEYTREEAEEALELAEEVLEFVEKLLKE 121

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 568988119    6 VRVTVLRGcvGCRTVAVPATATGRDLKERIFAETSFPVAEQRLWRGDREIPDWIKIGDL-TSKTCHLFV 73
Cdd:cd17039     1 ITVKTLDG--KTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYgIKDGSTIHL 67

DnaJ molecular chaperone homology domain;

                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 568988119   4331 ESERKKIIRRLYLKWHPDKNPENHDIANEVFKhlqnEIN 4369
Cdd:smart00271   15 LDEIKKAYRKLALKYHPDKNPGDKEEAEEKFK----EIN 49

chaperone protein DnaJ; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568988119 4331 ESERKKIIRRLYLKWHPDKNPENHDIANEVFKHLQNEINRL---EKQAFLDQ 4379
Cdd:PRK14282   18 QEEIKRAYKRLVKEWHPDRHPENRKEAEQKFKEIQEAYEVLsdpQKRAMYDR 69