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 157824184 250 IDDSVPTTKIQIRLADGSRLIQRFNSTHRILDVRDFIVQSRPEFATTDFILVTSFPSKELTDESVTLQDADILNTVILQQ 329
Cdd:cd17161    1 IDDSVPTTKIQIRLADGSRLIQRFNQSHRIHDIRQFIVQSRPVFAASDFLLVTTFPNKELTDESQTLQEADILNTVILQR 80

                 ..
gi 157824184 330 LK 331
Cdd:cd17161   81 LK 82

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2B (UBXN2B) and similar proteins; UBXN2B, also termed NSFL1 cofactor p37, or p97 cofactor p37, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN2B is an adaptor protein of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. UBXN2B forms a tight complex with p97 in the cytosol and localizes to the Golgi and endoplasmic reticulum (ER).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157824184 250 IDDSVPTTKIQIRLADGSRLIQRFNSTHRILDVRDFIVQSRPEFATTDFILVTSFPSKELTDESVTLQDADILNTVILQQ 329
Cdd:cd17161    1 IDDSVPTTKIQIRLADGSRLIQRFNQSHRIHDIRQFIVQSRPVFAASDFLLVTTFPNKELTDESQTLQEADILNTVILQR 80

                 ..
gi 157824184 330 LK 331
Cdd:cd17161   81 LK 82

SEP domain; The SEP domain is named after Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47. In p47, the SEP domain has been shown to bind to and inhibit the cysteine protease cathepsin L. Most SEP domains are succeeded closely by a UBX domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157824184  146 LRLWSNGFSLDDGELRPYSDPTNAQFLESVKRGEIPLELQRLVHGSQVSLDMEDHQDQEYIKPRLRFKAFSGEGQ 220
Cdd:pfam08059   1 LTFWRNGFSVDDGPLRRYDDPANAEFLEAINRGEAPLELLNVAPGQGVDVNLEDRRDEDYVPPKKKYKPFSGSGR 75

Domain present in ubiquitin-regulatory proteins; Present in FAF1 and Shp1p.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 157824184   256 TTKIQIRLADGSRLIQRFNSTHRILDVRDFIVQSrPEFATTDFILVTSFPSKELT--DESVTLQDADIL-NTVILQQ 329
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVSAA-LGDGNDPFTLNSPFPRRTFTkdDYSKKLLELALLpSSTLVLE 76

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2B (UBXN2B) and similar proteins; UBXN2B, also termed NSFL1 cofactor p37, or p97 cofactor p37, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN2B is an adaptor protein of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. UBXN2B forms a tight complex with p97 in the cytosol and localizes to the Golgi and endoplasmic reticulum (ER).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157824184 250 IDDSVPTTKIQIRLADGSRLIQRFNSTHRILDVRDFIVQSRPEFATTDFILVTSFPSKELTDESVTLQDADILNTVILQQ 329
Cdd:cd17161    1 IDDSVPTTKIQIRLADGSRLIQRFNQSHRIHDIRQFIVQSRPVFAASDFLLVTTFPNKELTDESQTLQEADILNTVILQR 80

                 ..
gi 157824184 330 LK 331
Cdd:cd17161   81 LK 82

Domain present in Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157824184   140 QDVQILLRLWSNGFSLDDGELRPYSDPTNAQFLESVKRGEIPLELQRLVHGSQVSLDMEDHQDQEYIKPRLRFKAFSGEG 219
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDGPLRTYDDPENAEFLESIRRGEAPLELLRVAKGQPVNVDVEDHRDEDYVAPPGAFKPFSGSG 80

                           90
                   ....*....|...
gi 157824184   220 QKLGSLTPEIVST 232
Cdd:smart00553  81 QKLGSPGPQSLST 93

Ubiquitin regulatory domain X (UBX) found in UBX domain-containing proteins UBXN2A, UBXN2B, NSFL1C/UBXN2C, and similar proteins; This family includes UBX domain-containing proteins UBXN2A, UBXN2B, and NSFL1C/UBXN2C, which contain a SEP (Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47) domain, and a ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold at the C-terminus. UBX domain participates broadly in the regulation of protein degradation. UBXN2A, UBXN2B, and UBXN2C function as the adaptor proteins of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 157824184 258 KIQIRLADGSRLIQRFNSTHRILDVRDFIVQSRPEFAtTDFILVTSFPSKELTDESVTLQDADILNTVILQQ 329
Cdd:cd01770    1 SIQIRLADGSRLVARFNLTHTVGDIRQFIDSARPGYS-RPFVLMTGFPPKELTDESQTLEEAGLLNAVVVQK 71

UBX domain; This domain is present in ubiquitin-regulatory proteins and is a general Cdc48-interacting module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 157824184  255 PTTKIQIRLADGSRLIQRFNSTHRILDVRDFIVQSRPEFATTdFILVTSFPSKELT--DESVTLQDADIL-NTVILQQL 330
Cdd:pfam00789   3 DVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNRYDDLEP-FSLNTPFPRRPLTdlDYSKTLKEAGLLpNSTLVLEP 80

Domain present in ubiquitin-regulatory proteins; Present in FAF1 and Shp1p.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 157824184   256 TTKIQIRLADGSRLIQRFNSTHRILDVRDFIVQSrPEFATTDFILVTSFPSKELT--DESVTLQDADIL-NTVILQQ 329
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVSAA-LGDGNDPFTLNSPFPRRTFTkdDYSKKLLELALLpSSTLVLE 76

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 4 (UBXN4) and similar proteins; UBXN4, also termed ERAD (endoplasmic-reticulum-associated protein degradation) substrate erasing protein (erasin), or UBX domain-containing protein 2 (UBXD2), or UBXDC1, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN4 is an endoplasmic reticulum (ER) localized protein that interacts with p97 (also known as VCP or Cdc48) via its UBX domain. Erasin exists in a complex with other p97/VCP-associated factors involved in endoplasmic-reticulum-associated protein degradation (ERAD). p97 is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. The overexpression of UBXN4 increases degradation of a classical ERAD substrate and UBXN4 levels are increased in ER stressed cells. Anti-UBXN4 staining is increased in neuropathological lesions in brains of patients with Alzheimer's disease.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157824184 256 TTKIQIRLADGSRLIQRFNSTHRILDVRDFIVQsRPEFATTDFILVTSFPSKELTDE--SVTLQD 318
Cdd:cd16117    1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQ-TVGPAYGPFSLATTFPRREFTDDdyQKTLLE 64

Ubiquitin regulatory domain X (UBX) found in FAS associated factor 1 (FAF1, also known as UBXN3A) and similar proteins; UBX domain-containing protein 3A (UBXN3A),also termed UBX domain-containing protein 12 (UBXD12), or FAF1, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. In addition, FAF1 contains two tandem ubiquitin-like (Ubl) domains, which shows high structural similarity with UBX domain. FAF1 functions as a cofactor of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. This family corresponds to UBX domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 157824184 255 PTTKIQIRLADGSRLIQRFNSTHRILDVRDFIvqSRPEFATTDFILVTSFPSKELT--DESVTLQDADI 321
Cdd:cd01771    3 PISKLRFRLPGGEFLTRRFLASEPLQVLLNFV--ASKGYPPDEYKLLTTFPRRDLTqlDPSKTLEELKL 69

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 8 (UBXN8) and similar proteins; UBXN8, also termed reproduction 8 protein (Rep8), or UBX domain-containing protein 6 (UBXD6), or D8S2298E, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN8 functions as a cofactor of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. UBXN8 is a transmembrane protein that localizes to the endoplasmic reticulum (ER) membrane with its UBX domain facing the cytoplasm. It facilitates efficient ER-associated degradation (ERAD) by tethering p97 to the ER membrane.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157824184 256 TTKIQIRLADGSRLIQRFNSTHRILDVRDFI--VQSRPEFATtdfiLVTSFPSKELTDES-VTLQDADILNTVIL 327
Cdd:cd01774    2 AVTIALRFPGGRVHRRRFLTTENIQVLLDWMtkLGYHQTLYT----LSTTYPRTILSDDAdKTLEDLGITKDVAL 72

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 7 (UBXN7) and similar proteins; UBXN7, also termed UBX domain-containing protein 7 (UBXD7), belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN7 functions as a ubiquitin-binding adaptor that mediates the interaction between the AAA+ ATPase p97 (also known as VCP or Cdc48) and the transcription factor HIF1-alpha. It binds only to the active, NEDD8- or Rub1-modified form of cullins. In addition to having a UBX domain, UBXD7 contains a ubiquitin-associated (UBA), ubiquitin-associating (UAS), and ubiquitin-interacting motif (UIM) domains. Either UBA or UIM could serve as a docking site for neddylated-cullins. UBA domain is required for binding ubiquitylated-protein substrates, while the UIM motif is responsible for the binding to cullin RING ligases (CRLs), and the UBX domain is essential for p97 binding.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157824184 257 TKIQIRLADGSRLIQRFNSTHRILDVRDFIvqSRPEFATTDFILVTSFPSKELT--DESVTLQDA 319
Cdd:cd01773    2 SKLMLRFPDGKREQLSLPASAKLKALVKYV--SSKGYPNERYELVTNFPRRKLShlDYDITLKEA 64