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 1736318434 490 QHLLRVAYQDPSTGCTSKTLAVPPGSSIATLSQLCATKFRVTQPDAFGLFLYKDQGYHRLPPEALAHRLPA-------TG 562
Cdd:cd17215     1 QNFLRVAYQDPSSGCTSKTLAVPPSATVADLNQLCATKFKVTQPETYGIFLYKEQGYQRLPPDALPQRIKAqlkekgsTF 80

                  ....*...
gi 1736318434 563 YLIYRRAE 570
Cdd:cd17215    81 YFVYQRAE 88

Ras-associating (RA) domain found in Ras and Rab interactor 1 (Rin1); Rin1, also termed Ras inhibitor JC99, or Ras interaction/interference protein 1, is a downstream Ras effector that represents a unique class of Ras effector connected to two independent signaling pathways. The first effector pathway is the direct activation of RAB5-mediated endocytosis and the second pathway involves direct activation of ABL tyrosine kinase activity. Rin1 functions as a guanine nucleotide exchange factor (GEF) for RAB5 GTPases. The RAB5 GEF activity of Rin1 promotes early endosome fusion, an early event in transit to the lysosome. Rin1 binds the SH3 and SH2 domains of ABL proteins, ABL1 and ABL2, and activates their tyrosine kinase activity. Rin1 contains SH2 and proline-rich domains in the N-terminal region, and RH, VPS9, and RA domains in the C-terminal region. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1736318434 490 QHLLRVAYQDPSTGCTSKTLAVPPGSSIATLSQLCATKFRVTQPDAFGLFLYKDQGYHRLPPEALAHRLPA-------TG 562
Cdd:cd17215     1 QNFLRVAYQDPSSGCTSKTLAVPPSATVADLNQLCATKFKVTQPETYGIFLYKEQGYQRLPPDALPQRIKAqlkekgsTF 80

                  ....*...
gi 1736318434 563 YLIYRRAE 570
Cdd:cd17215    81 YFVYQRAE 88

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.)

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1736318434  489 FQHLLRVAYQDPStGCTSKTLAVPPGSSIATLSQLCATKFRVT-QPDAFGLFLYKDQG-YHRLPPEALAHRL-------- 558
Cdd:smart00314   1 DTFVLRVYVDDLP-GGTYKTLRVSSRTTARDVIQQLLEKFHLTdDPEEYVLVEVLPDGkERVLPDDENPLQLqklwprrg 79

                           90
                   ....*....|
gi 1736318434  559 PATGYLIYRR 568
Cdd:smart00314  80 PNLRFVLRKR 89

Ras-associating (RA) domain found in Ras and Rab interactor 1 (Rin1); Rin1, also termed Ras inhibitor JC99, or Ras interaction/interference protein 1, is a downstream Ras effector that represents a unique class of Ras effector connected to two independent signaling pathways. The first effector pathway is the direct activation of RAB5-mediated endocytosis and the second pathway involves direct activation of ABL tyrosine kinase activity. Rin1 functions as a guanine nucleotide exchange factor (GEF) for RAB5 GTPases. The RAB5 GEF activity of Rin1 promotes early endosome fusion, an early event in transit to the lysosome. Rin1 binds the SH3 and SH2 domains of ABL proteins, ABL1 and ABL2, and activates their tyrosine kinase activity. Rin1 contains SH2 and proline-rich domains in the N-terminal region, and RH, VPS9, and RA domains in the C-terminal region. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1736318434 490 QHLLRVAYQDPSTGCTSKTLAVPPGSSIATLSQLCATKFRVTQPDAFGLFLYKDQGYHRLPPEALAHRLPA-------TG 562
Cdd:cd17215     1 QNFLRVAYQDPSSGCTSKTLAVPPSATVADLNQLCATKFKVTQPETYGIFLYKEQGYQRLPPDALPQRIKAqlkekgsTF 80

                  ....*...
gi 1736318434 563 YLIYRRAE 570
Cdd:cd17215    81 YFVYQRAE 88

Ras-associating (RA) domain of Ras and Rab interactor (Rin) protein family; Family of Ras-interaction/interference (Rin) proteins, also known as Ras and Rab interactors, is composed of Rin1, Rin2, and Rin3, which have multifunctional domains, including SH2 and proline-rich domains in the N-terminal region, and RH, VPS9, and RA domains in the C-terminal region. 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 the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. The RA domains of Rin1, Rin2, and Rin3 are well conserved and they all have Ras binding characteristics.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1736318434 490 QHLLRVAYQDPSTGC-TSKTLAVPPGSSIATLSQLCATKFRVTQPDAFGLFLYKDQGYHRLPPEALAHRLPA-------- 560
Cdd:cd01776     1 QGFLRVAVPDENNGSiVSKTLPVRPSMTAREVCKMIAHKFRVTNPQDYGLFLLVDGEEIQLEDNECPQLIKGellatskk 80

                          90
                  ....*....|
gi 1736318434 561 TGYLIYRRAE 570
Cdd:cd01776    81 PCYFAYKRID 90

Ras-associating (RA) domain found in Ras and Rab interactor 3 (Rin3); Rin3, also termed Ras interaction/interference protein 3, is a RAS effector and a RAB5-activating guanine nucleotide exchange factor (GEF) specifically for GTPase Rab31. It functions as a negative regulator of mast cell responses to Stem Cell Factor (SCF). Rin3 contains the Vps9p-like guanine nucleotide exchange factor and Ras-association (RA) domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1736318434 490 QHLLRVAYQDPstGCTSKTLAVPPGSSIATLSQLCATKFRVTQPDAFGLFLYKDQGYHRLPPEALAHRL 558
Cdd:cd16130     1 QDFISVSFLEP--GSNTRTLAIRPDTTAEDLCKQCAEKFEVLDPENYGLFVLVDGRCLQLADDALPHHI 67

Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. Previous studies showed that RIN1 interacts with EGF receptors via its SH2 domain and regulates trafficking and degradation of EGF receptors via its interaction with STAM, indicating a vital role for RIN1 in regulating endosomal trafficking of receptor tyrosine kinases (RTKs). RIN1 was first identified as a Ras-binding protein that suppresses the activated RAS2 allele in S. cerevisiae. RIN1 binds to the activated Ras through its carboxyl-terminal domain and this Ras-binding domain also binds to 14-3-3 proteins as Raf-1 does. The SH2 domain of RIN1 are thought to interact with the phosphotyrosine-containing proteins, but the physiological partners for this domain are unknown. The proline-rich domain in RIN1 is similar to the consensus SH3 binding regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                          10
                  ....*....|....*...
gi 1736318434   1 MFQDLVQLICGYCRTRDI 18
Cdd:cd10393    80 TFPDLVQLICAYCHTRDI 97