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 68342026 250 IDDSMPTTKIQIRLADGSRLVQRFNSTHRILDVRDFIVRSRPEFATTDFILVTSFPSKELTDETVTLQEADILNTVILQQ 329
Cdd:cd17161   1 IDDSVPTTKIQIRLADGSRLIQRFNQSHRIHDIRQFIVQSRPVFAASDFLLVTTFPNKELTDESQTLQEADILNTVILQR 80

                ..
gi 68342026 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 68342026 250 IDDSMPTTKIQIRLADGSRLVQRFNSTHRILDVRDFIVRSRPEFATTDFILVTSFPSKELTDETVTLQEADILNTVILQQ 329
Cdd:cd17161   1 IDDSVPTTKIQIRLADGSRLIQRFNQSHRIHDIRQFIVQSRPVFAASDFLLVTTFPNKELTDESQTLQEADILNTVILQR 80

                ..
gi 68342026 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 68342026   146 LKLWRNGFSLDDGELRPYSDPTNAQFLESVKRGETPLELQRLVHGAQVNLDMEDHQDQEYIKPRLRFKAFSGEGQ 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 68342026    256 TTKIQIRLADGSRLVQRFNSTHRILDVRDFiVRSRPEFATTDFILVTSFPSKELT--DETVTLQEADIL-NTVILQQ 329
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEF-VSAALGDGNDPFTLNSPFPRRTFTkdDYSKKLLELALLpSSTLVLE 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 68342026 250 IDDSMPTTKIQIRLADGSRLVQRFNSTHRILDVRDFIVRSRPEFATTDFILVTSFPSKELTDETVTLQEADILNTVILQQ 329
Cdd:cd17161   1 IDDSVPTTKIQIRLADGSRLIQRFNQSHRIHDIRQFIVQSRPVFAASDFLLVTTFPNKELTDESQTLQEADILNTVILQR 80

                ..
gi 68342026 330 LK 331
Cdd:cd17161  81 LK 82

Ubiquitin regulatory domain X (UBX) found in NSFL1 cofactor (also known as UBX domain-containing protein 2C (UBXN2C) and similar proteins; UBXN2C, also termed NSFL1C, or NSFL1 cofactor p47, or p97 cofactor p47, UBX1, or UBXD10, 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. UBXN2C is a major adaptor 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 main role of the UBXN2C/p97 complex is in regulation of membrane fusion events. It plays an essential role in the reassembly of Golgi stacks at the end of mitosis. UBXN2C also functions as an essential factor for Golgi membrane fusion, which associates with the nuclear factor-kappaB essential modulator (NEMO) subunit of the IkappaB kinase (IKK) complex upon tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 stimulation, induces the lysosome-dependent degradation of polyubiquitinated NEMO without p97, and thus inhibits IKK activation. Moreover, UBXN2C regulates a membrane fusion process, which is required by the maintenance of the endoplasmic reticulum (ER) network, through phosphorylation by Cdc2 kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68342026 250 IDDSMPTTKIQIRLADGSRLVQRFNSTHRILDVRDFIVRSRPEFATTDFILVTSFPSKELTDETVTLQEADILNTVILQQ 329
Cdd:cd17162   1 INDSEPVTNIQIRLADGGRLVQKFNHSHRIRDIRLFIVDARPAMAATSFVLMTTFPNKELTDENQTLKEANLLNAVIVQR 80

                ..
gi 68342026 330 LK 331
Cdd:cd17162  81 LK 82

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 68342026 258 KIQIRLADGSRLVQRFNSTHRILDVRDFIVRSRPEFAtTDFILVTSFPSKELTDETVTLQEADILNTVILQQ 329
Cdd:cd01770   1 SIQIRLADGSRLVARFNLTHTVGDIRQFIDSARPGYS-RPFVLMTGFPPKELTDESQTLEEAGLLNAVVVQK 71

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 68342026   255 PTTKIQIRLADGSRLVQRFNSTHRILDVRDFIVRSRPEFATTdFILVTSFPSKELTDETV--TLQEADIL-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 68342026    256 TTKIQIRLADGSRLVQRFNSTHRILDVRDFiVRSRPEFATTDFILVTSFPSKELT--DETVTLQEADIL-NTVILQQ 329
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEF-VSAALGDGNDPFTLNSPFPRRTFTkdDYSKKLLELALLpSSTLVLE 76

Ubiquitin regulatory domain X (UBX) found in FAS associated factor 2 (FAF2, also known as UBXN3B) and similar proteins; UBX domain-containing protein 3B (UBXN3B), also termed protein ETEA, or FAF2, or UBX domain-containing protein 8 (UBXD8), 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. FAF2 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 p97-UBXD8 complex destabilizes mRNA by promoting release of ubiquitinated the RNA-binding protein HuR from messenger ribonucleoprotein (mRNP). Moreover, FAF2 is the translation product of a highly expressed gene in the T-cells and eosinophils of atopic dermatitis patients compared with those of normal individuals. A yeast two-hybrid assay showed that FAF2 can interact with Fas.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 68342026 257 TKIQIRLADGSRLVQRFNSTHRILDVRDFIVrSRPEfATTDFILVTSFPSKELTDETV-------TLQEADILNTVIL 327
Cdd:cd16120   1 VKILFKLPNGTRLERRFLKSDSLKVLYDFVF-SHED-SPDKFQLVTNFPRRVLPCQPTeeqpnppTLEEAGLGKSEVL 76

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 68342026 255 PTTKIQIRLADGSRLVQRFNSTHRILDVRDFIvrSRPEFATTDFILVTSFPSKELT--DETVTLQEADI 321
Cdd:cd01771   3 PISKLRFRLPGGEFLTRRFLASEPLQVLLNFV--ASKGYPPDEYKLLTTFPRRDLTqlDPSKTLEELKL 69

Ubiquitin regulatory domain X (UBX) 2 found in UBX domain protein 9 (UBXN9, UBXD9, or ASPSCR1) and similar proteins; UBXN9, also termed tether containing UBX domain for GLUT4 (TUG), or alveolar soft part sarcoma chromosomal region candidate gene 1 protein (ASPSCR1), or alveolar soft part sarcoma locus (ASPL), or renal papillary cell carcinoma protein 17 (RCC17), belongs to the UBXD family of proteins that contains two ubiquitin regulatory domains 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, UBXN9 contains an N-terminal ubiquitin-like (Ubl) domain. UBXN9 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. However, high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers; the extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers.UBXN9 is involved in insulin-stimulated redistribution of the glucose transporter GLUT4, assembly of the Golgi apparatus. In addition to GLUT4, UBXN9 also controls vesicle translocation by interacting with insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. UBXN9 and its budding yeast ortholog, Ubx4p, are multifunctional proteins that share some, but not all functions. Yeast Ubx4p is important for endoplasmic reticulum-associated protein degradation (ERAD) but UBXN9 appears not to share this function.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 68342026 259 IQIRLADGSRLVQRFNSTHRILDVRDFIVRSRPEfATTDFILVTSFPSKELTDETVTLQEAD 320
Cdd:cd16118   3 IRVQFPDRLVLQAFFRPLETVRALYDFVKSHLAD-PDLPFYLYTTPPKRVLKDKNKTLYQAG 63