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 25777680   1 MSLNKDGSYTGFIKVQLKLVRPVSVPSSKKPPSLQDARRGPGRGTSVRRRTSFYLPKDAVKHLHVLSRTRAREVIEALLR 80
Cdd:cd17218  23 MSLNKDGSYTGFIKVQLKLVRPVSVPANKKPSSIQDSRKGSGRSQPVKRRTSFYLPKDTVKHLHISSKTRASEVIEALLK 102

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 25777680  81 KFLVVDDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKEN 135
Cdd:cd17218 103 KFTVVDNPRKFALFERTEKDDQVYLRKLSDDEQPLYLRLLAGPNEKTLSFVLKEN 157

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777680   1 MSLNKDGSYTGFIKVQLKLVRPVSVPSSKKPPSLQDARRGPGRGTSVRRRTSFYLPKDAVKHLHVLSRTRAREVIEALLR 80
Cdd:cd17218  23 MSLNKDGSYTGFIKVQLKLVRPVSVPANKKPSSIQDSRKGSGRSQPVKRRTSFYLPKDTVKHLHISSKTRASEVIEALLK 102

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 25777680  81 KFLVVDDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKEN 135
Cdd:cd17218 103 KFTVVDNPRKFALFERTEKDDQVYLRKLSDDEQPLYLRLLAGPNEKTLSFVLKEN 157

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 25777680     49 RRTSFYLPKDAVKHLHVLSRTRAREVIEALLRKFLVVDDPRKFALFeraERHGQVYLRKLLDDEQPLRLRLLAGPSDKAL 128
Cdd:smart00314   6 RVYVDDLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDDPEEYVLV---EVLPDGKERVLPDDENPLQLQKLWPRRGPNL 82

                   ....*...
gi 25777680    129 SFVLKEND 136
Cdd:smart00314  83 RFVLRKRD 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 25777680   144 AFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEAL 183
Cdd:pfam16517   1 AFSLPELENFLRILDEEEEREIQQIRRKYTALRQKLQQAL 40

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777680   1 MSLNKDGSYTGFIKVQLKLVRPVSVPSSKKPPSLQDARRGPGRGTSVRRRTSFYLPKDAVKHLHVLSRTRAREVIEALLR 80
Cdd:cd17218  23 MSLNKDGSYTGFIKVQLKLVRPVSVPANKKPSSIQDSRKGSGRSQPVKRRTSFYLPKDTVKHLHISSKTRASEVIEALLK 102

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 25777680  81 KFLVVDDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKEN 135
Cdd:cd17218 103 KFTVVDNPRKFALFERTEKDDQVYLRKLSDDEQPLYLRLLAGPNEKTLSFVLKEN 157

Ras-associating (RA) domain of Ras-association domain family 5 (RASSF5); RASSF5, also called New ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is a member of a family of six related RASSF1-6 proteins (the classical RASSF proteins) and is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. All transcripts variants of RASSF5 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. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777680   1 MSLNKDGSYTGFIKVQLKLVRPVSVPSSKKPPSLQDArrGPGRGTSvrRRTSFYLPKDAVKHLHVLSRTRAREVIEALLR 80
Cdd:cd17220  22 MKLSPDGTYTGFIKVHLKLRRPVTVPAGIRPQSIYEV--NPADTTD--KRTSFYLPLDAIKQLHISSTTTVSEVIQGLLK 97

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 25777680  81 KFLVVDDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKEN 135
Cdd:cd17220  98 KFMVVDNPQKFALFKRMRKDGQVLFQKLPLTEYPLYLRLLAGPDTDVLSFVLKEN 152

C-terminal SARAH domain found in Ras-association domain-containing protein 1 (RASSF1); RASSF1 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 is required for death receptor-dependent apoptosis. It mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1, with both localized to microtubules and involved in regulation of growth and migration. With the exception of some minor splice variants (RASSF1F and RASSF1G), RASSF1 contains an RA domain and a C-terminal SARAH (Salvador-RassF-Hippo) 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. This model corresponds to the SARAH domain of RASSF1.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 25777680 141 NWDAFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEALHAC 186
Cdd:cd21890   1 NWDAFSMPELQNFLRILQREEEEHVRQILQRYTRCREKMQEALASR 46

C-terminal SARAH domain found in Ras-association domain proteins, RASSF1, RASSF3, and RASSF5; The RASSF subfamily 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). Classical RASSF proteins interact either directly or indirectly with activated Ras. Ras proteins are small GTPases that are involved in cellular signal transduction. They seem to modulate some of the growth inhibitory responses mediated by Ras and may serve as tumor suppressor genes. RASSF1-6 contains a conserved SARAH (Salvador-RassF-Hippo) 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. This model corresponds to the SARAH domain of RASSF1, RASSF3, and RASSF5. It is a characteristic coiled-coil structure that is important in signal-transduction networks. The central function of the SARAH domain is the mediation of homo- and heterodimerization between SARAH domain-containing proteins.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 25777680 141 NWDAFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEALHA 185
Cdd:cd21885   1 LWEAFSLPELENFLKILDREEKEYIEQIREKYRIYRKKLQRRLDE 45

C-terminal SARAH domain found in Ras-association domain-containing protein 5 (RASSF5); RASSF5, also called New ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), 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 be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. RASSF5 is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. All transcript variants of RASSF5 contain 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. 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. This model corresponds to the SARAH domain of RASSF5, that mediates homo- and heterodimerization.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 25777680 138 GEVNWDAFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEAL 183
Cdd:cd21892   1 GEVEWDAFSVPELQNFLRILEKEEQDKIQQVQKKYAKFRQKLQDAL 46

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 25777680   144 AFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEAL 183
Cdd:pfam16517   1 AFSLPELENFLRILDEEEEREIQQIRRKYTALRQKLQQAL 40

Ras-associating (RA) domain found in Ras-association domain family members, RASSF2, RASSF4, and RASSF6; The RASSF family of proteins shares a conserved RalGDS/AF6 RA domain either in the C-terminus (RASSF1-6) or N-terminus (RASSF7-10). The classical family members (RASSF1-6) contain a conserved SARAH (Salvador/RASSF/Hpo) motif adjacent to the RA domain that functions as scaffolding and regulatory interactions. The RA domain of the classical RASSF protein family has the 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 protein family seem to modulate some of the growth inhibitory responses mediated by Ras and may serve as tumor suppressor genes. This family contains RASSF2, RASSF4, and RASSF6.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777680  49 RRTSFYLPK-DAVKHLHVLSRTRAREVIEALLRKFLVVDDPRKFALF---ERAERhgqvylRKLLDDEQPLRLRLLAGPS 124
Cdd:cd01784   2 RKTSVFTPPyGSVTNVRVTSLMTTPEVIKLLLEKFKVENSPEEFALYvvkDSGER------RRLKDDDYPLLTRVLLGPS 75

                        90
                ....*....|..
gi 25777680 125 DKALSFVLKEND 136
Cdd:cd01784  76 EDVAKIFIMERA 87

C-terminal SARAH domain found in scaffold protein salvador (Sav), Ras-association domain proteins, and mammalian STE20-like protein kinases (MST); The SARAH (Salvador-RassF-Hippo) domain family includes scaffold protein salvador (Sav), Ras-association domain proteins (RASSF1-6), and mammalian STE20-like protein kinase (MST) subfamily members (MST1-2 and Hippo). Sav is a scaffold protein mainly found in metazoans. Drosophila melanogaster Sav, also called Shar-pei (SHRP), promotes both cell cycle exit and apoptosis in Drosophila. It plays a key role in the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. Human protein salvador homolog 1, also called 45 kDa WW domain protein (WW45), acts as a mammalian sterile 20-like kinase 1 (MST1)-binding protein required to enhance MST1-mediated apoptosis. It is a regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway. Classical RASSF proteins interact either directly or indirectly with activated Ras. Ras proteins are small GTPases that are involved in cellular signal transduction. They seem to modulate some of the growth inhibitory responses mediated by Ras and may serve as tumor suppressor genes. RASSF1-6 contains a conserved SARAH motif adjacent to the RA domain that functions in scaffolding and regulatory interactions. MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 and MST2 are STE20 family stress-activated, pro-apoptotic serine/threonine-protein kinases which, following caspase-cleavage, enter the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. They are key components of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Hippo (Hpo), also called STE20-like kinase MST (dMST), is the Drosophila homolog of STE20-like protein kinases, MST1 and MST2. It is a STE20 family serine/threonine-protein kinase that functions as a tumor suppressor by restricting cell proliferation and promotes apoptosis in conjunction with salvador and warts. Hpo also plays a key role in the Hippo/SWH signaling pathway. This model corresponds to the C-terminal SARAH domain, a characteristic coiled-coil structure. It is a small helical module that is important in signal-transduction networks. The central function of the SARAH domain seems to be the mediation of homo- and heterodimerization between SARAH domain-containing proteins.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 25777680 142 WDAFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEALHA 185
Cdd:cd21883   2 LKNFSLPELQMFLKMLDPEEEREIEQLVKKYTAYRQAILDALEE 45

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 25777680  57 KDAVKHLHVLSRTRAREVIEALLRKFLVvdDPR-----KFALFERAERHGQvylRKLLDDEQPLRLRLLAGPSDKALSFV 131
Cdd:cd01782  34 KVATKCIRVSSTATTQDVIETLIEKFRP--DMRmlsnpRYSLYEVHPNGEE---RKLDDDEKPLVVQLNWNKDDREGRFL 108

                ..
gi 25777680 132 LK 133
Cdd:cd01782 109 LK 110

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 25777680  58 DAVKHLHVLSRTRAREVIEALLRKFLVVD-DPRKFALFERAERHGQVYlRKLLDDEQPLRLRL 119
Cdd:cd01783  14 VAYKSIPVTKETTVEEVIKEALPKFGLQDeDPEDFRLVEVLMDKGVVE-RVMLRDECPWLILL 75