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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1240374839 169 LVRVYDHNICAASNYKSLMLSSLTNCEEAIDLILaqNRKSREESA-NYGLFLTTPEAEAQIP 229
Cdd:cd17043     1 VLKVYDDDLAPGSAYKSILVSSTTTAREVVQLLL--EKYGLEEDPeDYSLYEVSEKQETERV 60

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1240374839   71 GVLKVYTSDIRQCTdYKTIRVSTKTTARNVIEMVLTKFKLTCrDPNLFELWMElttkaegKPVKTILRLENDAKPLELQR 150
Cdd:smart00314   3 FVLRVYVDDLPGGT-YKTLRVSSRTTARDVIQQLLEKFHLTD-DPEEYVLVEV-------LPDGKERVLPDDENPLQLQK 73

                           90
                   ....*....|...
gi 1240374839  151 CHP--AGMSRFLL 161
Cdd:smart00314  74 LWPrrGPNLRFVL 86

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1240374839 169 LVRVYDHNICAASNYKSLMLSSLTNCEEAIDLILaqNRKSREESA-NYGLFLTTPEAEAQIP 229
Cdd:cd17043     1 VLKVYDDDLAPGSAYKSILVSSTTTAREVVQLLL--EKYGLEEDPeDYSLYEVSEKQETERV 60

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1240374839   71 GVLKVYTSDIRQCTdYKTIRVSTKTTARNVIEMVLTKFKLTCrDPNLFELWMElttkaegKPVKTILRLENDAKPLELQR 150
Cdd:smart00314   3 FVLRVYVDDLPGGT-YKTLRVSSRTTARDVIQQLLEKFHLTD-DPEEYVLVEV-------LPDGKERVLPDDENPLQLQK 73

                           90
                   ....*....|...
gi 1240374839  151 CHP--AGMSRFLL 161
Cdd:smart00314  74 LWPrrGPNLRFVL 86

Ras-associating (RA) domain 2 found in diacylgylcerol kinase theta (DAGK-theta) and similar proteins; DAGK phosphorylates the second messenger diacylglycerol to phosphatidic acid as part of a protein kinase C pathway. DAGK-theta is characterized as a type V DAGK that has three cysteine-rich domains (all other isoforms have two), a proline/glycine-rich domain at its N-terminal, and a proposed Ras-associating (RA) domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. There are ten mammalian isoforms of DAGK have been identified to date, these are organized into five categories based on the domain architecture. DAGK-theta also contains a pleckstrin homology (PH) domain. The subcellular localization and the activity of DAGK-theta are regulated in a complex (stimulation- and cell type-dependent) manner. This family corresponds to the second RA domain of DAGK-theta.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1240374839  71 GVLKVYTSDIRQCTDYKTIRVSTKTTARNVIEMVLTKFKLTCRDPNLFEL 120
Cdd:cd01783     1 GYIRVYPGWLKVGVAYKSIPVTKETTVEEVIKEALPKFGLQDEDPEDFRL 50

Ras-associating (RA) domain 2 found in Afadin; Afadin, also termed ALL1-fused gene from chromosome 6 protein (AF-6), or canoe, is involved in many fundamental signaling cascades in cells. In addition, it is involved in oncogenesis and metastasis. Afadin has multiple domains: from the N-terminus to the C-terminus it has two Ras-associated (RA) domains, a forkhead-associated domain, a dilute domain, a PDZ domain, three proline-rich domains, and an F-actin binding domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. Afadin is abundant at cadherin-based adherens junctions in epithelial cells, endothelial cells, and fibroblasts. This family corresponds to the second RA domain of afadin.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1240374839  71 GVLKVYTSDIRQCTDYKTIRVSTKTTARNVIEMVLTKFKLTCRDPNLF-----ELWMELTTKAEGKPVKTILrLENDAKP 145
Cdd:cd01781     2 GTLKIYGDSLKPEVPYKTLLLSTNDTADFVVREALEKYGLEKENPKDYclvqvVLPPGGSPRLDGGGGKERI-LDDDECP 80

                  ....*...
gi 1240374839 146 LELQRCHP 153
Cdd:cd01781    81 LAILMRWP 88

Ras-associating (RA) domain found in Ras-association domain family members, RASSF1, RASSF3, and RASSF5; The RASSF family of proteins shares a conserved RalGDS/AF6 Ras association (RA) domain which is located either at the C-terminus (RASSF1-6, the classical group) or at the N-terminus (RASSF7-10). RASSF1-6 contains a conserved SARAH (Salvador/RASSF/Hpo) motif adjacent to the RA domain that functions in scaffolding and regulatory interactions. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Classical RASSF members interact either directly or indirectly with activated Ras. Ras proteins are small GTPases that are involved in cellular signal transduction. The classical RASSF proteins seem to modulate some of the growth inhibitory responses mediated by Ras and may serve as tumor suppressor genes. This family contains RASSF1, RASSF3, and RASSF5.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1240374839  87 KTIRVSTKTTARNVIEMVLTKFKLTcRDPNLFELWmELTTKAEGKpvKTILRLENDAKPLEL 148
Cdd:cd01778    55 KALHITSDTTAREVIEALLKKFKIT-DNPRKFALY-ERTHEEEGK--VKLRKLSDDERPLYL 112

Ras-associating (RA) domain 1 found in Afadin; Afadin, also termed ALL1-fused gene from chromosome 6 protein (AF-6), or canoe, is involved in many fundamental signaling cascades in cells. In addition, it is involved in oncogenesis and metastasis. Afadin has multiple domains: from the N-terminus to the C-terminus it has two Ras-associated (RA) domains, a forkhead-associated domain, a dilute domain, a PDZ domain, three proline-rich domains, and an F-actin-binding domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. Afadin is abundant at cadherin-based adherens junctions in epithelial cells, endothelial cells, and fibroblasts. This family corresponds to the first RA domain of afadin, which mediates its self-association.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1240374839  71 GVLKVYTSDIRQCTDYKTIRVSTKTTARNVIEMVLTKFK-----LTCRDPNLFELwmelttkaegKPVKTILRLENDAKP 145
Cdd:cd01782    22 GVMRFYFQDGGAKVATKCIRVSSTATTQDVIETLIEKFRpdmrmLSNPRYSLYEV----------HPNGEERKLDDDEKP 91

                  ....
gi 1240374839 146 LELQ 149
Cdd:cd01782    92 LVVQ 95