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 17568517 352 LLIRFPTGKKVI-KFNADDNIEKIFDEAMKSEMCPLFFQMHQSFPKKAVPCLPkwyfeilsaeelepkSECLSNNLTFQE 430
Cdd:cd16120   3 ILFKLPNGTRLErRFLKSDSLKVLYDFVFSHEDSPDKFQLVTNFPRRVLPCQP---------------TEEQPNPPTLEE 67

                        90
                ....*....|.
gi 17568517 431 AGITHGSMVYI 441
Cdd:cd16120  68 AGLGKSEVLFV 78

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17568517   268 DRSARNRVQNE-----------SRRLMEEQNREYQESLQR------DLERIAKSKSEEEAAKKAQEEEEQKQRDAEER 328
Cdd:pfam15709 331 EKASRDRLRAEraemrrleverKRREQEEQRRLQQEQLERaekmreELELEQQRRFEEIRLRKQRLEEERQRQEEEER 408

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17568517 352 LLIRFPTGKKVI-KFNADDNIEKIFDEAMKSEMCPLFFQMHQSFPKKAVPCLPkwyfeilsaeelepkSECLSNNLTFQE 430
Cdd:cd16120   3 ILFKLPNGTRLErRFLKSDSLKVLYDFVFSHEDSPDKFQLVTNFPRRVLPCQP---------------TEEQPNPPTLEE 67

                        90
                ....*....|.
gi 17568517 431 AGITHGSMVYI 441
Cdd:cd16120  68 AGLGKSEVLFV 78

UBA-like domain found in the NXF family of mRNA nuclear export factors and similar proteins; This family includes nuclear RNA export factors (NXF1/NXF2), FAS-associated factors (FAF1/2), tyrosyl-DNA phosphodiesterase 2 (TDP2), OTU domain-containing proteins (OTU7A/OTU7B), NSFL1 cofactor p47, defective in cullin neddylation protein 1 (DCN1)-like protein (DCNL1/DCNL2), yeast defective in cullin neddylation protein 1 (DCN1) and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. 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. 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. Its biological function remains unclear. TDP2 is a 5'-Tyr-DNA phosphodiesterase required for the efficient repair of topoisomerase II-induced DNA double strand breaks. OTU7A and OTU7B are zinc finger proteins that function as deubiquitinating enzymes. p47 is a major cofactor of the cytosolic AAA ATPase p97. It is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus. DCNL1 plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. The biological function of DCNL2 remains unclear. Yeast DCN1 is a scaffold-type E3 ligase for cullin neddylation. It can bind directly to cullins and the ubiquitin-like protein Nedd8-specific E2 (Ubc12), and regulate cullin neddylation and thus display ubiquitin ligase activity.

                        10        20        30
                ....*....|....*....|....*....|
gi 17568517  13 MEITNCEQAVAVDYLTRTNYDVEIAVRHFF 42
Cdd:cd14273   2 MEITGADPETARQYLESNNWDLEAAINLYF 31

UDM1 (ubiquitin-dependent DSB recruitment module 1) found in RING finger proteins RNF168, RNF169 and similar proteins; This model represents the UDM1 (ubiquitin-dependent double-strand break [DSB] recruitment module 1) found in RING finger proteins, RNF168 and RNF169. RNF168 is an E3 ubiquitin-protein ligase that promotes non-canonical K27 ubiquitination to signal DNA damage. It functions, together with RNF8, as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates such as H2A and H2AX. With H2AK13/15 ubiquitylation, it facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. In addition, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF169 is an uncharacterized E3 ubiquitin-protein ligase paralogous to RNF168. It functions as a negative regulator of the DNA damage signaling cascade. RNF169 recognizes polyubiquitin structures but does not itself contribute to double-strand break (DSB)-induced chromatin ubiquitylation. It contributes to the regulation of DSB repair pathway utilization via functionally competing with recruiting repair factors, 53BP1 and RAP80-BRCA1, for association with RNF168-modified chromatin, independent of its catalytic activity, limiting the magnitude of the RNF8/RNF168-dependent signaling response to DSBs. The UDM1 domain comprises LRM1 (LR motif 1), UMI (ubiquitin-interacting motif [UIM]- and MIU-related UBD) and MIU1 (motif interacting with ubiquitin 1). Mutations of Ub-interacting residues in UDM1 have little effect on the accumulation of RNF168 to DSB sites, suggesting that it may not be the main site of binding ubiquitylated and polyubiquitylated targets.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 17568517 288 REYQESLQRDLERIAKSKSEEEAA-----KKAQEEEEQKQRDAEERL 329
Cdd:cd22249   9 EEYEAQLKKLEEERRKEREEEEKAseeliRKLQEEEERQRKREREEQ 55

cell envelope integrity inner membrane protein TolA; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17568517  266 DADRSARNR---VQNESRRLMEEQNREYQESLQRDLERIAKSKSEEEAAKKAQEEEEQKQRDAEERLNTVETYK 336
Cdd:PRK09510  73 SAKRAEEQRkkkEQQQAEELQQKQAAEQERLKQLEKERLAAQEQKKQAEEAAKQAALKQKQAEEAAAKAAAAAK 146

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17568517   264 ADDADRSARNRVQNESRRLMEEQNRE--YQESLQRDLERIAKSKSEEEAAKKA----QEEEEQKQRDAEER 328
Cdd:TIGR02794  62 AAKKEQERQKKLEQQAEEAEKQRAAEqaRQKELEQRAAAEKAAKQAEQAAKQAeekqKQAEEAKAKQAAEA 132

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17568517 352 LLIRFPTGKKVI-KFNADDNIEKIFDEAMKSEMCPLFFQMHQSFPKKAVPCLPkwyfeilsaeelepkSECLSNNLTFQE 430
Cdd:cd16120   3 ILFKLPNGTRLErRFLKSDSLKVLYDFVFSHEDSPDKFQLVTNFPRRVLPCQP---------------TEEQPNPPTLEE 67

                        90
                ....*....|.
gi 17568517 431 AGITHGSMVYI 441
Cdd:cd16120  68 AGLGKSEVLFV 78

Ubiquitin regulatory domain X (UBX) structurally similar to a beta-grasp ubiquitin-like fold; The UBXD family of proteins 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. Members in this family function as cofactors 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. Based on domain composition, UBXD proteins can be divided into two main groups, with and without ubiquitin-associated (UBA) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17568517 352 LLIRFPTGKKVI-KFNADDNIEKIFDEAM-KSEMCPLFFQMHQSFPKKAVPCLPKwyfeilsaeelepkseclsnNLTFQ 429
Cdd:cd01767   2 IQIRLPDGSRIQrRFSKSDTLQDLYDFVEsNLGDSPSSFSLVTSFPRRVLTDEDS--------------------DKTLE 61

                        90
                ....*....|..
gi 17568517 430 EAGITHGSMVYI 441
Cdd:cd01767  62 ELGLTPNAVLFV 73

UBA-like domain found in yeast defective in cullin neddylation protein 1 (DCN1) and similar proteins; DCN1 is a scaffold-type E3 ligase for cullin neddylation. It can bind directly to cullins and the ubiquitin-like protein Nedd8-specific E2 (Ubc12), and regulate cullin neddylation and thus display ubiquitin ligase activity. It contains an N-terminal ubiquitin-associated (UBA)-like domain and a unique C-terminal PONY domain that is essential for the neddylation function of DCN1.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 17568517   7 ATIAQMMEITNCEQAVAVDYLTRTNYDVEIAVRHFF 42
Cdd:cd14352   1 ELIKQFREITATSPEVARDYLQRSNWNLNYAVDDFY 36

UBA-like domain found in yeast UBX domain-containing protein 1 (Ubx1) and similar proteins; Ubx1, also called suppressor of high-copy PP1 protein (Shp1), is the substrate-recruiting cofactor of AAA-adenosine triphosphatase Cdc48 in Saccharomyces cerevisiae. In concert with ubiquitin-like Atg8, Cdc48 and Ubx1 are involved in the regulation of autophagosome biogenesis. Ubx1 also functions as a regulator of phosphoprotein phosphatase 1 (PP1) with differential effects on glycogen metabolism, meiotic differentiation, and mitotic cell cycle progression. All family members contain an N-terminal ubiquitin-associated (UBA)-like domain.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 17568517   8 TIAQMMEITNCEQAVAVDYLTRTNYDVEIAVRHFF 42
Cdd:cd14351   3 AIQQFMELTGASPEVAQQYLEEYGGDLNDAINAYF 37

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17568517   269 RSARNRVQNESRRLMEEQNREYQESLQRDLERI-AKSKSEEEAAKKAQEEEEQKQRDAEE 327
Cdd:pfam13904 123 SASKSLAKPERKVSQEEAKEVLQEWERKKLEQQqRKREEEQREQLKKEEEEQERKQLAEK 182

Coiled-coil domain-containing protein 50 N-terminus;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17568517   256 DLALIDLIADDADRSARNRVQNESRRLMEEQN---REYQESLQRDLE-RIAKSKSEEEAAKKAQEEEEQKQR 323
Cdd:pfam15295  52 DIRVAKQLQEEEELQAQTLFQRRLAQLEEQDEeiaKEIQEELQREAEeRRRREEEDEEIARQLQERERERER 123

cell envelope integrity inner membrane protein TolA; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17568517  266 DADRSARNR---VQNESRRLMEEQNREYQESLQRDLERIAKSKSEEEAAKKAQEEEEQKQRDAEERLNTVETYK 336
Cdd:PRK09510  73 SAKRAEEQRkkkEQQQAEELQQKQAAEQERLKQLEKERLAAQEQKKQAEEAAKQAALKQKQAEEAAAKAAAAAK 146

DNA repair exonuclease SbcCD ATPase subunit [Replication, recombination and repair];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17568517 229 FVIRGNSLTRKLLIDDLSNPESVSTNIDLALidliaDDADRSAR-NRVQNESRRLMEEQNREYQESLQR-----DLERIA 302
Cdd:COG0419  45 YALYGKARSRSKLRSDLINVGSEEASVELEF-----EHGGKRYRiERRQGEFAEFLEAKPSERKEALKRllgleIYEELK 119

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 17568517 303 KS-KSEEEAAKKAQEEEEQKQRDAEERLNTVETYK--RTISGDTTLSTGSHDLL 353
Cdd:COG0419 120 ERlKELEEALESALEELAELQKLKQEILAQLSGLDpiETLSGGERLRLALADLL 173

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17568517   271 ARNRVQNESRRLMEEQNREYQESLQRDLERiakSKSEEEAAKKAQEEEEQKQRDAEERLNTVE 333
Cdd:pfam05672  41 ERLRKEELRRRAEEERARREEEARRLEEER---RREEEERQRKAEEEAEEREQREQEEQERLQ 100

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 17568517   272 RNRVQNESRRLMEEQNREYQESLQRDLERIAKSKSEEEAakKAQEEEEQKQRDAEERL 329
Cdd:pfam05672  70 RRREEEERQRKAEEEAEEREQREQEEQERLQKQKEEAEA--KAREEAERQRQEREKIM 125

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17568517   272 RNRVQNESRRLMEEQNR--EYQESLQRDLERIAKSKSEE--EAAKKAQEEEEQKQRDAEER 328
Cdd:pfam15709 437 RKKQQEEAERAEAEKQRqkELEMQLAEEQKRLMEMAEEErlEYQRQKQEAEEKARLEAEER 497

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17568517   258 ALIDLIADDADRSARNRVQnESRRLMEEQNREYQESLQRDLERIAKSKSEEEAAKKAQ----------EEEEQKQRDAEE 327
Cdd:pfam15346  26 EELEKRKDEIEAEVERRVE-EARKIMEKQVLEELEREREAELEEERRKEEEERKKREElerileennrKIEEAQRKEAEE 104

                  ....*.
gi 17568517   328 RLNTVE 333
Cdd:pfam15346 105 RLAMLE 110