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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723986   5 YKEDHPFEYRKKEGEKIRKKYPDRVPVIVEKAPKARVPDLDKRKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNNTI 84
Cdd:cd16127     1 YKEDHPFEKRRSEGEKIRKKYPDRVPVIVEKAPKARVADLDKKKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNNVI 80

                          90
                  ....*....|..
gi 1391723986  85 PPTSATMGQLYE 96
Cdd:cd16127    81 PPTSATMGQLYQ 92

ubiquitin-like (Ubl) domain found in gamma-aminobutyric acid receptor-associated protein (GABARAP) and similar proteins; sub-family of the autophagy-related 8 (ATG8) protein family; GABARAP (also termed GABA(A) receptor-associated protein, ATG8A, or MM46) has been implicated in intracellular protein trafficking. It is a cytosolic protein, localized to transport vesicles, the Golgi network and the endoplasmic reticulum. It interacts with the intracellular domain of the gamma2 subunit of GABA(A) receptors, and thus, functions as a trafficking modulator implicated in the intracellular trafficking of GABA(A) receptor. GABARAP also acts as a Ubl modifier belonging to the ATG8 (autophagy-related 8) protein family which is essential for autophagosome biogenesis and maturation. GABARAP recruits phosphatidylinositol 4-kinase II alpha (PI4KIIalpha) as a specific downstream effector, and regulates phosphatidylinositol 4-phosphate (PI4P)-dependent autophagosome lysosome fusion. This sub-family also includes GABARAPL1 (also termed GABA(A) receptor-associated protein-like, or GEC1), GABARAPL2/GATE-16, and GABARAPL3. GABARAPL1 has been involved in the intracellular transport of receptors via interactions with tubulin and GABA(A) or kappa opioid receptors. GABARAPL1 is also a Ubl modifier that functions as a mediator involved in androgen-regulated autophagy process. It is transcriptionally modulated by androgen receptor (AR) and has a repressive role in autophagy. In addition, GABARAPL1 is required for increased membrane expression of epidermal growth factor receptor (EGFR) during hypoxia, suggesting a possible role in the trafficking of these membrane proteins. GABARAPL1 may also play a key role in several important biological processes such as cancer or neurodegenerative diseases. Low expression of GABARAPL1 is associated with poor prognosis of patients with hepatocellular carcinoma.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723986   5 YKEDHPFEYRKKEGEKIRKKYPDRVPVIVEKAPKARVPDLDKRKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNNTI 84
Cdd:cd16127     1 YKEDHPFEKRRSEGEKIRKKYPDRVPVIVEKAPKARVADLDKKKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNNVI 80

                          90
                  ....*....|..
gi 1391723986  85 PPTSATMGQLYE 96
Cdd:cd16127    81 PPTSATMGQLYQ 92

microtubule-associated protein (MAP); Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723986   5 YKEDHPFEYRKKEGEKIRKKYPDRVPVIVEKAPKARvpdlDKRKYL-VPSDLTVGQFYFLIRKRIHLRPEDaLFFFVNNT 83
Cdd:PTZ00380    4 YHSSNPVEARRAECARLQAKYPGHVAVVVEAAEKAG----SKVHFLaLPRDATVAELEAAVRQALGTSAKK-VTLAIEGS 78

                          90
                  ....*....|.
gi 1391723986  84 IPPTSATMGQL 94
Cdd:PTZ00380   79 TPAVTATVGDI 89

ubiquitin-like (Ubl) domain found in gamma-aminobutyric acid receptor-associated protein (GABARAP) and similar proteins; sub-family of the autophagy-related 8 (ATG8) protein family; GABARAP (also termed GABA(A) receptor-associated protein, ATG8A, or MM46) has been implicated in intracellular protein trafficking. It is a cytosolic protein, localized to transport vesicles, the Golgi network and the endoplasmic reticulum. It interacts with the intracellular domain of the gamma2 subunit of GABA(A) receptors, and thus, functions as a trafficking modulator implicated in the intracellular trafficking of GABA(A) receptor. GABARAP also acts as a Ubl modifier belonging to the ATG8 (autophagy-related 8) protein family which is essential for autophagosome biogenesis and maturation. GABARAP recruits phosphatidylinositol 4-kinase II alpha (PI4KIIalpha) as a specific downstream effector, and regulates phosphatidylinositol 4-phosphate (PI4P)-dependent autophagosome lysosome fusion. This sub-family also includes GABARAPL1 (also termed GABA(A) receptor-associated protein-like, or GEC1), GABARAPL2/GATE-16, and GABARAPL3. GABARAPL1 has been involved in the intracellular transport of receptors via interactions with tubulin and GABA(A) or kappa opioid receptors. GABARAPL1 is also a Ubl modifier that functions as a mediator involved in androgen-regulated autophagy process. It is transcriptionally modulated by androgen receptor (AR) and has a repressive role in autophagy. In addition, GABARAPL1 is required for increased membrane expression of epidermal growth factor receptor (EGFR) during hypoxia, suggesting a possible role in the trafficking of these membrane proteins. GABARAPL1 may also play a key role in several important biological processes such as cancer or neurodegenerative diseases. Low expression of GABARAPL1 is associated with poor prognosis of patients with hepatocellular carcinoma.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723986   5 YKEDHPFEYRKKEGEKIRKKYPDRVPVIVEKAPKARVPDLDKRKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNNTI 84
Cdd:cd16127     1 YKEDHPFEKRRSEGEKIRKKYPDRVPVIVEKAPKARVADLDKKKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNNVI 80

                          90
                  ....*....|..
gi 1391723986  85 PPTSATMGQLYE 96
Cdd:cd16127    81 PPTSATMGQLYQ 92

ubiquitin-like (Ubl) domain found in gamma-aminobutyric acid receptor-associated protein (GABARAP); GABARAP (also termed GABA(A) receptor-associated protein, ATG8A, or MM46) has been implicated in intracellular protein trafficking. It is a cytosolic protein that is localized to transport vesicles, the Golgi network and the endoplasmic reticulum. It interacts with the intracellular domain of the gamma2 subunit of GABA(A) receptors, and thus functions as a trafficking modulator implicated in the intracellular trafficking of GABA(A) receptor. GABARAP also acts as a Ubl modifier belonging to the ATG8 (autophagy-related 8) protein family, which is essential for autophagosome biogenesis and maturation. GABARAP recruits phosphatidylinositol 4-kinase II alpha (PI4KIIalpha) as a specific downstream effector, and regulates phosphatidylinositol 4-phosphate (PI4P)-dependent autophagosome lysosome fusion.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723986   2 KFQYKEDHPFEYRKKEGEKIRKKYPDRVPVIVEKAPKARVPDLDKRKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVN 81
Cdd:cd17232     1 KFVYKEEHPFEKRRSEGEKIRKKYPDRVPVIVEKAPKARIGDLDKKKYLVPSDLTVGQFYFLIRKRIHLRAEDALFFFVN 80

                          90
                  ....*....|....*
gi 1391723986  82 NTIPPTSATMGQLYE 96
Cdd:cd17232    81 NVIPPTSATMGQLYQ 95

ubiquitin-like (Ubl) domain found in GABA type A receptor associated protein like 2 (GABARAPL2, also known as GATE16); Autophagy is an essential intracellular process that targets large protein complexes, bacterial pathogens, and organelles for degradation. GABARAPL2 (GABA type A receptor associated protein like 2), also known as GATE-16 (golgi-associated adenosine triphosphatase enhancer of 16 kDa), has a ubiquitin-like (Ubl) domain and is a sub-family of the autophagy-related 8 (ATG8) protein family. GABARAPL2 participates to the autophagosome maturation, and seems to be involved in constitutive transport under normal conditions and in autophagic processes during stress. GABARAPL2 is characterized as a membrane transport modulator that controls intra-Golgi transport by interacting with NSF and Golgi v-SNARE GOS-28.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723986   5 YKEDHPFEYRKKEGEKIRKKYPDRVPVIVEKAPKARVPDLDKRKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNNTI 84
Cdd:cd17163     1 FKEEHSLEQRCAESAKIRAKYPDRIPVIVEKVPKSQIPDIDKRKFLVPSDITVAQFMWIIRKRIQLPSEKAIFLFVGKVL 80

                          90
                  ....*....|..
gi 1391723986  85 PPTSATMGQLYE 96
Cdd:cd17163    81 PQSSATMGQLYE 92

ubiquitin-like (Ubl) domain found in autophagy-related 8 (ATG8) and similar proteins; The ATG8 family of proteins constitute a single member in Saccharomyces cerevisiae, Atg8p, and multiple homologs in higher eukaryotes, they are multifunctional ubiquitin-like (Ubl) key regulators of autophagy. The ATG8 system is a Ubl conjugation system that is essential for autophagosome formation. In the ATG8 system, a cysteine protease (ATG4) cleaves a C-terminal arginine from ATG8, and then the exposed C-terminal glycine is conjugated to phosphatidylethanolamine (PE) by ATG7, an E1-like enzyme, and ATG3, an E2-like enzyme. The mammalian ATG8 family is classified into three subfamilies: i) MAP1LC3 (microtubule associated protein 1 light chain 3) which includes MAP1LC3A, MAP1LC3B, MAP1LC3B2, and MAP1LC3C, ii) GABARAP (GABA type A receptor associated protein) which includes GABARAP, GABARAPL1, and GABARAPL3, and iii) GABARAPL2 (GABA type A receptor associated protein like 2), also known as GATE-16 (golgi-associated adenosine triphosphatase enhancer of 16 kDa).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723986  27 DRVPVIVEKAPKARVPDLDKRKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNNTIPPTSATMGQLYE 96
Cdd:cd16108     1 DRIPVIVEKAPKSDLPDIDKKKFLVPSDLTVGQFMYIIRKRIKLSPEKAIFLFVNNTLPPTSALMSEVYE 70

ubiquitin-like (Ubl) domain found in microtubule associate protein 1 light chain 3 (MAP1LC3); Autophagy is an essential intracellular process that targets large protein complexes, bacterial pathogens, and organelles for degradation. MAP1LC3 (also known as LC3) has a ubiquitin-like (Ubl) fold and belongs to the ATG8 autophagy protein family. A Ubl conjugation of MAP1LC3 by the phospholipid phosphatidylethanolamine (PE) is an essential process for the formation of autophagosomes. MAP1LC3 is cleaved by the cysteine protease ATG4 and is then conjugated with PE by E1-like enzyme ATG7 and ATG3, an E2-like enzyme. The Ubl conversion of MAP1LC3 is known as a marker of autophagy-induction. This sub-family includes MAP1LC3A, MAP1LC3B, and MAP1LC3C, each encoded by a different MAP1LC3 gene.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723986  14 RKKEGEKIRKKYPDRVPVIVEKAPKAR-VPDLDKRKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNN-TIPPTSATM 91
Cdd:cd16129     2 RKKDVEEIREKHPNKIPVIIERYKGEKqLPLLDKTKFLVPDHVTMSELVKIIRRRLQLNPTQAFFLLVNQrSMVSVSTPM 81

                  ....*
gi 1391723986  92 GQLYE 96
Cdd:cd16129    82 SEVYR 86

ubiquitin-like (Ubl) domain found in microtubule associate protein 1 light chain 3A (MAP1LC3A); Autophagy is an essential intracellular process that targets large protein complexes, bacterial pathogens, and organelles for degradation. MAP1LC3A is belong to MAP1LC3 (short name LC3) family proteins. MAP1LC3 has a ubiquitin-like fold (Ubl) that belongs to the autophagy-related 8 (ATG8) protein family. A Ubl conjugation of MAP1LC3 by the phospholipid phosphatidylethanolamine (PE) is an essential process for the formation of autophagosomes. MAP1LC3 is cleaved by cysteine protease ATG4 and then conjugated with PE by E1-like enzyme ATG7 and ATG3, an E2-like enzyme. The Ubl conversion of MAPLC3 is known as a marker of autophagy-induction. MAP1LC3A staining patterns are used for different cancer diagnostic.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1391723986   5 YKEDHPFEYRKKEGEKIRKKYPDRVPVIVEKAP-KARVPDLDKRKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVN-N 82
Cdd:cd17234     4 FKQRRSFADRCKEVQQIRDQHPSKIPVIIERYKgEKQLPVLDKTKFLVPDHVNMSELVKIIRRRLQLNPTQAFFLLVNqH 83

                          90
                  ....*....|....
gi 1391723986  83 TIPPTSATMGQLYE 96
Cdd:cd17234    84 SMVSVSTPIADIYE 97

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises 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 proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1391723986  38 KARVPDLDKRKYLVPSDLTVGQFYFLIRKRIHLrPEDALFFFVNNTIPPTSATMGQ 93
Cdd:cd00196     2 KVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGL-PPDVIRLLFNGQVLDDLMTAKQ 56

Ubiquitin-like autophagy protein Apg12; In yeast, 15 Apg proteins coordinate the formation of autophagosomes. Autophagy is a bulk degradation process induced by starvation in eukaryotic cells. The Apg12 system is one of the ubiquitin-like protein conjugation systems conserved in eukaryotes. It was first discovered in yeast during systematic analyses of the apg mutants defective in autophagy. Covalent attachment of Apg12-Apg5 is essential for autophagy.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1391723986  37 PKARVPDLDKRKYLVPSDLTVGQFYFLIRKRIHLRPEDALFFFVNNTIPPT-SATMGQLYE 96
Cdd:pfam04110   8 AIGDAPILKKSKFKVNPSQTFASVILFLKKFLKLQASDSLFLYVNNSFAPSpDQIVGNLYE 68