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 393715063 175 NHETSIFIPAFESETKVRVNSNMRTEEVIKQLLQKFKIENSPQDFALHIIFATGEQRRLKKTDIPLLQRLLQGPSEKNAR 254
Cdd:cd17223    1 NYKTSVFTPAFGSETKVRINSNMTTQEVIKQLLQKFKIENSPNEFALYIIHATGEKKRLKNTDFPLWERLLQGPSGKIAK 80

                 ....*..
gi 393715063 255 IFLMDKD 261
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 393715063 175 NHETSIFIPAFESETKVRVNSNMRTEEVIKQLLQKFKIENSPQDFALHIIFATGEQRRLKKTDIPLLQRLLQGPSEKNAR 254
Cdd:cd17223    1 NYKTSVFTPAFGSETKVRINSNMTTQEVIKQLLQKFKIENSPNEFALYIIHATGEKKRLKNTDFPLWERLLQGPSGKIAK 80

                 ....*..
gi 393715063 255 IFLMDKD 261
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 393715063  174 YNHETSIFIPAFESETK---VRVNSNMRTEEVIKQLLQKFKIENSPQDFAL-HIIFATGEQRRLKKTDIPLLQRLLQGPS 249
Cdd:pfam00788   1 DDGVLKVYTEDGKPGTTyktILVSSSTTAEEVIEALLEKFGLEDDPRDYVLvEVLERGGGERRLPDDECPLQIQLQWPRD 80

                          90
                  ....*....|...
gi 393715063  250 EKNARIFLMDKDA 262
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 393715063  274 NFHFSLLESILQRLNEEEKREIQRIVTKFNKEKAIILKCL 313
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 393715063 175 NHETSIFIPAFESETKVRVNSNMRTEEVIKQLLQKFKIENSPQDFALHIIFATGEQRRLKKTDIPLLQRLLQGPSEKNAR 254
Cdd:cd17223    1 NYKTSVFTPAFGSETKVRINSNMTTQEVIKQLLQKFKIENSPNEFALYIIHATGEKKRLKNTDFPLWERLLQGPSGKIAK 80

                 ....*..
gi 393715063 255 IFLMDKD 261
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 393715063 175 NHETSIFIPAFESETKVRVNSNMRTEEVIKQLLQKFKIENSPQDFALHIIFATGEQRRLKKTDIPLLQRLLQGPSEKNAR 254
Cdd:cd17221    1 NHKTSVFTPAYGSVTNVRINSTMTTPQVLKLLLNKFKIENSAEEFALYIVHTSGEKQKLKATDYPLIARILQGPCEQVSK 80

                 ....*..
gi 393715063 255 IFLMDKD 261
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 393715063 271 QYINFHFSLLESILQRLNEEEKREIQRIVTKFNKEKAIILKCLQNK 316
Cdd:cd21895    1 QYINFELPFLESILQKLNEEEEREIQKIVAKYKKEKAILLQCLRSK 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 393715063   172 HFYNHETSIFIPAFESETKVRVNSNMRTEEVIKQLLQKFKIENSPQDFALHIIFATGEQRRLKKTDIPLLQRLLQGPSEK 251
Cdd:smart00314   1 DTFVLRVYVDDLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDDPEEYVLVEVLPDGKERVLPDDENPLQLQKLWPRRGP 80

                           90
                   ....*....|
gi 393715063   252 NARIFLMDKD 261
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 393715063  274 NFHFSLLESILQRLNEEEKREIQRIVTKFNKEKAIILKCL 313
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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 393715063 177 ETSIFIPAFESETkVRVNSNMRTEEVIKQLLQKFKIENSPQDFAL----HIIFATGEQRRLKKTDIPLLQRLLQGPSEKN 252
Cdd:cd01778   44 RTSFYLPKDTVKA-LHITSDTTAREVIEALLKKFKITDNPRKFALyertHEEEGKVKLRKLSDDERPLYLCLLWGSQGDS 122

                 ....*
gi 393715063 253 ARIFL 257
Cdd:cd01778  123 KSFVL 127

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 393715063 189 TK-VRVNSNMRTEEVIKQLLQKFKIEN---SPQDFALHIIFATGEQRRLKKTDIPLLQRL 244
Cdd:cd01782   37 TKcIRVSSTATTQDVIETLIEKFRPDMrmlSNPRYSLYEVHPNGEERKLDDDEKPLVVQL 96

C-terminal SARAH domain found in Ras-association domain-containing protein 4 (RASSF4); RASSF4 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 also functions as a KRAS effector protein. RASSF4 is broadly expressed in normal tissues. Its expression is reduced in tumor cell lines and primary tumors by promoter specific hypermethylation. RASSF4 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 RASSF4.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 393715063 271 QYINFHFSLLESILQRLNEEEKREIQRIVTKFNKEKAIILKCLQNK 316
Cdd:cd21894    1 QYIKFEMPVLDSFVEKLKEEEEREIIKLTRKYSALRSMILQQLEQL 46

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing proteins ARAP1, ARAP2, ARAP3, and similar proteins; ARAPs are phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating proteins (GAPs). They contain multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 393715063 191 VRVNSNMRTEEVIKQLLQKFKIENSPQDFALHIIFATGE-QRRLKKTDIPL 240
Cdd:cd17113   20 IKVTPTMTAEEVVEQALNKKNLGGPEGNWALFEVIEDGGlERPLHESEKVL 70

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 393715063 196 NMRTEEVIKQLLQKFKIENsPQDFALHIIfATGEQRRLKKTDIPLL 241
Cdd:cd01776   26 SMTAREVCKMIAHKFRVTN-PQDYGLFLL-VDGEEIQLEDNECPQL 69