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 568936272 133 DHETSIFTPTFGSETKVRANSIMRTEEVIKQLLQKFKIENSPRDFALYIIFGTGEQRKLKKTDVPLLQRLLQGPSKSNAR 212
Cdd:cd17223    1 NYKTSVFTPAFGSETKVRINSNMTTQEVIKQLLQKFKIENSPNEFALYIIHATGEKKRLKNTDFPLWERLLQGPSGKIAK 80

                 ....*..
gi 568936272 213 IFLMDKD 219
Cdd:cd17223   81 MFLMDKD 87

Ras-associating (RA) domain found in Ras-association domain-containing protein 6 (RASSF6); RASSF6 is a member of a family of six related classical RASSF1-6 proteins and is expressed as four transcripts via alternative splicing. All transcripts variant of RASSF6 contain the RA and SARAH domains. The RA domain of the classical RASSF protein family has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. RA domains mediate interactions with Ras and other small GTPases, SARAH domains mediate protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF6 is ubiquitiated and degraded by interacting with MDM2 to stabilize P53 and regulates apoptosis and cell cycle. RASSF6 is a tumor suppressor protein and is epigenetically silenced in childhood leukemia and neuroblastomas. Overexpression of RASSF6 causes apoptosis in HeLa cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568936272 133 DHETSIFTPTFGSETKVRANSIMRTEEVIKQLLQKFKIENSPRDFALYIIFGTGEQRKLKKTDVPLLQRLLQGPSKSNAR 212
Cdd:cd17223    1 NYKTSVFTPAFGSETKVRINSNMTTQEVIKQLLQKFKIENSPNEFALYIIHATGEKKRLKNTDFPLWERLLQGPSGKIAK 80

                 ....*..
gi 568936272 213 IFLMDKD 219
Cdd:cd17223   81 MFLMDKD 87

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568936272  132 YDHETSIFTP--TFGSETK-VRANSIMRTEEVIKQLLQKFKIENSPRDFALY-IIFGTGEQRKLKKTDVPLLQRLLQGPS 207
Cdd:pfam00788   1 DDGVLKVYTEdgKPGTTYKtILVSSSTTAEEVIEALLEKFGLEDDPRDYVLVeVLERGGGERRLPDDECPLQIQLQWPRD 80

                          90
                  ....*....|...
gi 568936272  208 KSNARIFLMDKDA 220
Cdd:pfam00788  81 ASDSRFLLRKRDD 93

Novel Ras effector 1 C-terminal SARAH (Sav/Rassf/Hpo) domain; The Nore1-SARAH, C-terminal, domain of Nore1, the tumour-suppressor, a novel Ras effector, has a characteriztic coiled-coil structure. It is a small helical module that is important in signal-transduction networks. The recombinant SARAH domain of Nore1 crystallizes as an anti-parallel homodimer with representative characteriztics of coiled coils. The central function of the SARAH domain seems to be the mediation of homo- and hetero-oligomerization between SARAH domain-containing proteins. Nore1 forms homo- and hetero complexes through its C-terminal SARAH (Sav/Rassf/Hpo) domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568936272  232 NFHFSFLESILQRLDEEEKMEIERIMAKFNTERAFILKCL 271
Cdd:pfam16517   1 AFSLPELENFLRILDEEEEREIQQIRRKYTALRQKLQQAL 40

Ras-associating (RA) domain found in Ras-association domain-containing protein 6 (RASSF6); RASSF6 is a member of a family of six related classical RASSF1-6 proteins and is expressed as four transcripts via alternative splicing. All transcripts variant of RASSF6 contain the RA and SARAH domains. The RA domain of the classical RASSF protein family has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. RA domains mediate interactions with Ras and other small GTPases, SARAH domains mediate protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF6 is ubiquitiated and degraded by interacting with MDM2 to stabilize P53 and regulates apoptosis and cell cycle. RASSF6 is a tumor suppressor protein and is epigenetically silenced in childhood leukemia and neuroblastomas. Overexpression of RASSF6 causes apoptosis in HeLa cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568936272 133 DHETSIFTPTFGSETKVRANSIMRTEEVIKQLLQKFKIENSPRDFALYIIFGTGEQRKLKKTDVPLLQRLLQGPSKSNAR 212
Cdd:cd17223    1 NYKTSVFTPAFGSETKVRINSNMTTQEVIKQLLQKFKIENSPNEFALYIIHATGEKKRLKNTDFPLWERLLQGPSGKIAK 80

                 ....*..
gi 568936272 213 IFLMDKD 219
Cdd:cd17223   81 MFLMDKD 87

Ras-associating (RA) domain found in Ras-association domain-containing protein 2 (RASSF2); RASSF2 is a member of a family of six related classical RASSF1-6 proteins. The RASSF2 gene is transcribed into two major isoforms (A and C). RASSF2 is structurally related to RASSF1A but unlike RASSF1A It is primarily a nuclear protein. RASSF2 contains the RA and SARAH domains. The RA domain of the classical RASSF protein family has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. RA domains mediate interactions with Ras and other small GTPases, and SARAH domains mediate protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF2 is inactivated in different cancers and cancer cell lines by promoter methylation and loss of expression, implicating the correlation and significance of RASSF2 in tumorigenesis. In addition to regulating apoptosis and proliferation RASSF2 may have other functions as RASSF2 knockout mice develop normally for the first two weeks but then develop growth retardation and die 4 weeks after birth.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568936272 133 DHETSIFTPTFGSETKVRANSIMRTEEVIKQLLQKFKIENSPRDFALYIIFGTGEQRKLKKTDVPLLQRLLQGPSKSNAR 212
Cdd:cd17221    1 NHKTSVFTPAYGSVTNVRINSTMTTPQVLKLLLNKFKIENSAEEFALYIVHTSGEKQKLKATDYPLIARILQGPCEQVSK 80

                 ....*..
gi 568936272 213 IFLMDKD 219
Cdd:cd17221   81 VFLMEKD 87

C-terminal SARAH domain found in Ras-association domain-containing protein 6 (RASSF6); RASSF6 is one of six related proteins, the classical RASSF proteins (RASSF1-6), that contain a conserved RalGDS/AF6 Ras association (RA) domain located towards the C-terminus. It acts as a tumor suppressor protein involved in the induction of apoptosis, through both caspase-dependent and caspase-independent pathways. RASSF6 may function as a Ras effector protein. It is ubiquitinated and degraded by interacting with MDM2 to stabilize P53, and it regulates apoptosis and the cell cycle. RASSF6 is expressed as four transcripts via alternative splicing. All transcript variants of RASSF6 contain the RA and SARAH (Salvador-RassF-Hippo) domains. The RA domain of the classical RASSF proteins has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. RA domains mediate interactions with Ras and other small GTPases. SARAH domains mediate protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. This model corresponds to the SARAH domain of RASSF6.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 568936272 230 YINFHFSFLESILQRLDEEEKMEIERIMAKFNTERAFILKCLQSK 274
Cdd:cd21895    2 YINFELPFLESILQKLNEEEEREIQKIVAKYKKEKAILLQCLRSK 46

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 568936272   130 HVYDHETSIFTPTFGSETKVRANSIMRTEEVIKQLLQKFKIENSPRDFALYIIFGTGEQRKLKKTDVPLLQRLLQGPSKS 209
Cdd:smart00314   1 DTFVLRVYVDDLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDDPEEYVLVEVLPDGKERVLPDDENPLQLQKLWPRRGP 80

                           90
                   ....*....|
gi 568936272   210 NARIFLMDKD 219
Cdd:smart00314  81 NLRFVLRKRD 90

Novel Ras effector 1 C-terminal SARAH (Sav/Rassf/Hpo) domain; The Nore1-SARAH, C-terminal, domain of Nore1, the tumour-suppressor, a novel Ras effector, has a characteriztic coiled-coil structure. It is a small helical module that is important in signal-transduction networks. The recombinant SARAH domain of Nore1 crystallizes as an anti-parallel homodimer with representative characteriztics of coiled coils. The central function of the SARAH domain seems to be the mediation of homo- and hetero-oligomerization between SARAH domain-containing proteins. Nore1 forms homo- and hetero complexes through its C-terminal SARAH (Sav/Rassf/Hpo) domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568936272  232 NFHFSFLESILQRLDEEEKMEIERIMAKFNTERAFILKCL 271
Cdd:pfam16517   1 AFSLPELENFLRILDEEEEREIQQIRRKYTALRQKLQQAL 40

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 568936272 152 NSIMRTEEVIKQLLQKFKIENSPRDFALY----IIFGTGEQRKLKKTDVPLLQRLLQGPSKSNARIFL 215
Cdd:cd01778   60 TSDTTAREVIEALLKKFKITDNPRKFALYerthEEEGKVKLRKLSDDERPLYLCLLWGSQGDSKSFVL 127

Ras-associating (RA) domain found in Ras-association domain-containing protein 1 (RASSF1); RASSF1 is a member of a family of six related RASSF1-6 proteins (the classical RASSF proteins). RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. With the exception of some minor splice variants (RASSF1F and RASSF1G), RASSF1 contains an RA domain and a C-terminal SARAH protein-protein interaction motif. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF1A and 1C are the most extensively studied RASSF1 with both localized to microtubules and involved in regulation of growth and migration.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 568936272 153 SIMRTEEVIKQLLQKFKIENSPRDFALYIIFGTGEQ---RKLKKTDVPLLQRLLQGPS 207
Cdd:cd17218   89 SKTRASEVIEALLKKFTVVDNPRKFALFERTEKDDQvylRKLSDDEQPLYLRLLAGPN 146

Ras-associating (RA) domain found in Ras-association domain-containing protein 3 (RASSF3); RASSF3 is a member of a family of six related classical RASSF1-6 proteins (the classical RASSF proteins). RASSF3 has three transcripts (A-C) due to alternative splicing of the exons. The RASSF3B and 3C isoforms are shorter than RASSF3A, and unlike RASSF3A do not contain the RA or SARAH domains. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF3A regulates apoptosis and cell cycle via p53 stabilization and possibly is involved in DNA repair.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568936272 135 ETSIFTPTfGSETKVRANSIMRTEEVIKQLLQKFKIENSPRDFALYIIFGTGEQR---KLKKTDVPLLQRLLQGPS 207
Cdd:cd17219   56 ETAFYLPK-GSVNTLHISSTNTVREVIEALLKKFLVADNPAKFALYKRCHKEDQVyacKLSDREHPLYLRLVAGPN 130

C-terminal SARAH domain found in Ras-association domain-containing protein 2 (RASSF2); RASSF2 is one of six related proteins, the classical RASSF proteins (RASSF1-6), that contain a conserved RalGDS/AF6 Ras association (RA) domain located towards the C-terminus. It acts as a potential tumor suppressor that may promote apoptosis and cell cycle arrest. It is a KRAS-specific effector protein. It stabilizes STK3/MST2 by protecting it from proteasomal degradation. The RASSF2 gene is transcribed into two major isoforms (A and C). RASSF2 is structurally related to RASSF1A but unlike RASSF1A, it is primarily a nuclear protein. RASSF2 contains the RA and SARAH (Salvador-RassF-Hippo) domains. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. RA domains mediate interactions with Ras and other small GTPases, and SARAH domains mediate protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. This model corresponds to the SARAH domain of RASSF2.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 568936272 230 YINFHFSFLESILQRLDEEEKMEIERIMAKFNTERAFILKCLQ 272
Cdd:cd21893    2 YIKFEMPVLKSFIQKLKEEEDREVKKLMRRYTVLRLMIEQRLQ 44