Ras-associating (RA) domain found in Ras-association domain-containing protein 4 (RASSF4); RASSF4 is a member of a family of six related classical RASSF1-6 proteins and is broadly expressed in normal tissues. RASSF4 expression is reduced in tumor cell lines and primary tumors by promoter specific hypermethylation. RASSF4 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. RASSF4 inhibits lung cancer cell proliferation and invasion.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23510360 175 NHKTSVFTPAYGSVTNVRVNSTMTTLQVLTLLLNKFRVEDGPSEFALYIVHESGERTKLKDCEYPLISRILHGPCEKIAR 254
Cdd:cd17222   1 NHKTSVFTPAYGSVTNVRVNSTMTTPQVLKLLLNKFRVENSPDEFALYLVHESGERTKLKDTEYPLISRILHGPCEKIAR 80

                ....*..
gi 23510360 255 IFLMEAD 261
Cdd:cd17222  81 IFLMETD 87

Ras-associating (RA) domain found in Ras-association domain-containing protein 4 (RASSF4); RASSF4 is a member of a family of six related classical RASSF1-6 proteins and is broadly expressed in normal tissues. RASSF4 expression is reduced in tumor cell lines and primary tumors by promoter specific hypermethylation. RASSF4 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. RASSF4 inhibits lung cancer cell proliferation and invasion.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23510360 175 NHKTSVFTPAYGSVTNVRVNSTMTTLQVLTLLLNKFRVEDGPSEFALYIVHESGERTKLKDCEYPLISRILHGPCEKIAR 254
Cdd:cd17222   1 NHKTSVFTPAYGSVTNVRVNSTMTTPQVLKLLLNKFRVENSPDEFALYLVHESGERTKLKDTEYPLISRILHGPCEKIAR 80

                ....*..
gi 23510360 255 IFLMEAD 261
Cdd:cd17222  81 IFLMETD 87

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 23510360    172 HFYNHKTSVFTPAYGSVTNVRVNSTMTTLQVLTLLLNKFRVEDGPSEFALYIVHESGERTKLKDCEYPLISRILHGPCEK 251
Cdd:smart00314   1 DTFVLRVYVDDLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDDPEEYVLVEVLPDGKERVLPDDENPLQLQKLWPRRGP 80

                           90
                   ....*....|
gi 23510360    252 IARIFLMEAD 261
Cdd:smart00314  81 NLRFVLRKRD 90

Ras-associating (RA) domain found in Ras-association domain-containing protein 4 (RASSF4); RASSF4 is a member of a family of six related classical RASSF1-6 proteins and is broadly expressed in normal tissues. RASSF4 expression is reduced in tumor cell lines and primary tumors by promoter specific hypermethylation. RASSF4 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. RASSF4 inhibits lung cancer cell proliferation and invasion.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23510360 175 NHKTSVFTPAYGSVTNVRVNSTMTTLQVLTLLLNKFRVEDGPSEFALYIVHESGERTKLKDCEYPLISRILHGPCEKIAR 254
Cdd:cd17222   1 NHKTSVFTPAYGSVTNVRVNSTMTTPQVLKLLLNKFRVENSPDEFALYLVHESGERTKLKDTEYPLISRILHGPCEKIAR 80

                ....*..
gi 23510360 255 IFLMEAD 261
Cdd:cd17222  81 IFLMETD 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 23510360 175 NHKTSVFTPAYGSVTNVRVNSTMTTLQVLTLLLNKFRVEDGPSEFALYIVHESGERTKLKDCEYPLISRILHGPCEKIAR 254
Cdd:cd17221   1 NHKTSVFTPAYGSVTNVRINSTMTTPQVLKLLLNKFKIENSAEEFALYIVHTSGEKQKLKATDYPLIARILQGPCEQVSK 80

                ....*..
gi 23510360 255 IFLMEAD 261
Cdd:cd17221  81 VFLMEKD 87

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 23510360 272 QYIKFEMPVLDSFVEKLKEEEEREIIKLTMKFQALRLTMLQRLEQL 317
Cdd:cd21894   1 QYIKFEMPVLDSFVEKLKEEEEREIIKLTRKYSALRSMILQQLEQL 46

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 23510360   174 YNHKTSVFTPAYGSVT---NVRVNSTMTTLQVLTLLLNKFRVEDGPSEFAL--YIVHESGERtKLKDCEYPLISRILHGP 248
Cdd:pfam00788   1 DDGVLKVYTEDGKPGTtykTILVSSSTTAEEVIEALLEKFGLEDDPRDYVLveVLERGGGER-RLPDDECPLQIQLQWPR 79

                          90
                  ....*....|.
gi 23510360   249 CEKIARIFLME 259
Cdd:pfam00788  80 DASDSRFLLRK 90

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 23510360 272 QYIKFEMPVLDSFVEKLKEEEEREIIKLTMKFQALRLTMLQRLEQL 317
Cdd:cd21893   1 QYIKFEMPVLKSFIQKLKEEEDREVKKLMRRYTVLRLMIEQRLQEI 46

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
                ....*....|....*....|....*....|....*....|...
gi 23510360 209 KFRVEDGPSEFAL-YIVHESGER--TKLKDCEYPLISRILHGP 248
Cdd:cd17220  98 KFMVVDNPQKFALfKRMRKDGQVlfQKLPLTEYPLYLRLLAGP 140

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 23510360 191 VRVNSTMTTLQVLTLLLNKFRVED---GPSEFALYIVHESGERTKLKDCEYPLI 241
Cdd:cd01782  40 IRVSSTATTQDVIETLIEKFRPDMrmlSNPRYSLYEVHPNGEERKLDDDEKPLV 93