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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119617542  51 KEEIKEKVHKYNLAVTDKLKMTLNSNGIYTGFIKVQMELCKPPQTSP------NSGKLSPSSNGCMNTLHISSTNTVGEV 124
Cdd:cd17219    1 KEEIKQKIQLYNLAVTDKLKMTLNSSGIYTGFIKVQMDLRRPITVRGgaagnnNNETAFYLPKGSVNTLHISSTNTVREV 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119617542 125 IEALLKKFLVTESPAKFALYKRCHREDQVYACKLSDREHPLYLRLVAGPRTDTLSFVLREH 185
Cdd:cd17219   81 IEALLKKFLVADNPAKFALYKRCHKEDQVYACKLSDREHPLYLRLVAGPNTDTLSFVLREH 141

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119617542  51 KEEIKEKVHKYNLAVTDKLKMTLNSNGIYTGFIKVQMELCKPPQTSP------NSGKLSPSSNGCMNTLHISSTNTVGEV 124
Cdd:cd17219    1 KEEIKQKIQLYNLAVTDKLKMTLNSSGIYTGFIKVQMDLRRPITVRGgaagnnNNETAFYLPKGSVNTLHISSTNTVREV 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119617542 125 IEALLKKFLVTESPAKFALYKRCHREDQVYACKLSDREHPLYLRLVAGPRTDTLSFVLREH 185
Cdd:cd17219   81 IEALLKKFLVADNPAKFALYKRCHKEDQVYACKLSDREHPLYLRLVAGPNTDTLSFVLREH 141

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 119617542   79 YTGFIKVQMELCKPPQTSpnsgklspssngcmNTLHISSTNTVGEVIEALLKKFLVTESPAKFALYKRCHREDQVYacKL 158
Cdd:pfam00788   1 DDGVLKVYTEDGKPGTTY--------------KTILVSSSTTAEEVIEALLEKFGLEDDPRDYVLVEVLERGGGER--RL 64

                          90       100
                  ....*....|....*....|....*...
gi 119617542  159 SDREHPLYLRLVAGPRTDTLSFVLREHE 186
Cdd:pfam00788  65 PDDECPLQIQLQWPRDASDSRFLLRKRD 92

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 119617542   112 TLHISSTNTVGEVIEALLKKFLVTESPAKFALYKR-CHREDQVyackLSDREHPLYLRLVAGPRTDTLSFVLREHE 186
Cdd:smart00314  19 TLRVSSRTTARDVIQQLLEKFHLTDDPEEYVLVEVlPDGKERV----LPDDENPLQLQKLWPRRGPNLRFVLRKRD 90

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119617542  51 KEEIKEKVHKYNLAVTDKLKMTLNSNGIYTGFIKVQMELCKPPQTSP------NSGKLSPSSNGCMNTLHISSTNTVGEV 124
Cdd:cd17219    1 KEEIKQKIQLYNLAVTDKLKMTLNSSGIYTGFIKVQMDLRRPITVRGgaagnnNNETAFYLPKGSVNTLHISSTNTVREV 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119617542 125 IEALLKKFLVTESPAKFALYKRCHREDQVYACKLSDREHPLYLRLVAGPRTDTLSFVLREH 185
Cdd:cd17219   81 IEALLKKFLVADNPAKFALYKRCHKEDQVYACKLSDREHPLYLRLVAGPNTDTLSFVLREH 141

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 119617542  49 LSKEEIKEKVHKYNLAVTDKLKMTLNSNGIYTGFIKVQMELCKP--------PQTSPNSGKLSPSSNGC----------- 109
Cdd:cd17218    1 LSQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPvsvpankkPSSIQDSRKGSGRSQPVkrrtsfylpkd 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119617542 110 -MNTLHISSTNTVGEVIEALLKKFLVTESPAKFALYKRCHREDQVYACKLSDREHPLYLRLVAGPRTDTLSFVLREH 185
Cdd:cd17218   81 tVKHLHISSKTRASEVIEALLKKFTVVDNPRKFALFERTEKDDQVYLRKLSDDEQPLYLRLLAGPNEKTLSFVLKEN 157

C-terminal SARAH domain found in Ras-association domain-containing protein 3 (RASSF3); RASSF3 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. 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 (Salvador-RassF-Hippo) domains. RASSF3A regulates apoptosis and the cell cycle via p53 stabilization and is possibly involved in DNA repair. 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 RASSF3.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 119617542 189 EWEAFSLPELQNFLRILDKEEDEQLQNLKRRYTAYRQKLEEALREV 234
Cdd:cd21891    1 MWEAFSLPELQNFLRILDKEEDEQLRSIKRRYNAYREKLEEALRGV 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 119617542 189 EWEAFSLPELQNFLRILDKEEDEQLQNLKRRYTAYRQKLEEALRE 233
Cdd:cd21885    1 LWEAFSLPELENFLKILDREEKEYIEQIREKYRIYRKKLQRRLDE 45

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 119617542  192 AFSLPELQNFLRILDKEEDEQLQNLKRRYTAYRQKLEEAL 231
Cdd:pfam16517   1 AFSLPELENFLRILDEEEEREIQQIRRKYTALRQKLQQAL 40

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 119617542 189 EWEAFSLPELQNFLRILDKEEDEQLQNLKRRYTAYRQKLEEALRE 233
Cdd:cd21883    1 QLKNFSLPELQMFLKMLDPEEEREIEQLVKKYTAYRQAILDALEE 45

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various 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 (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119617542 112 TLHISSTNTVGEVIEALLKKFLVTESPAKFALYKRCHREDQVYacKLSDREHPLYLRLVAGPRTDTLSFVLRE 184
Cdd:cd17043   17 SILVSSTTTAREVVQLLLEKYGLEEDPEDYSLYEVSEKQETER--VLHDDECPLLIQLEWGPQGTEFRFVLKR 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 119617542 108 GCMNTLHISSTNTVGEVIEALLKKFLVTESPAKFALYKRCHREDQVyacKLSDREHPLYLRLVAGP 173
Cdd:cd17223   12 GSETKVRINSNMTTQEVIKQLLQKFKIENSPNEFALYIIHATGEKK---RLKNTDFPLWERLLQGP 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119617542 106 SNGCMNTLHISSTNTVGEVIEALLKKFLVTESPAKFALYKrCHREDQvyACKLSDREHPLYLRLVAGP 173
Cdd:cd17222   10 AYGSVTNVRVNSTMTTPQVLKLLLNKFRVENSPDEFALYL-VHESGE--RTKLKDTEYPLISRILHGP 74

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 119617542 193 FSLPELQNFLRILDKEEDEQLQNLKRRYTAYRQKLEEALREV 234
Cdd:cd21893    5 FEMPVLKSFIQKLKEEEDREVKKLMRRYTVLRLMIEQRLQEI 46

C-terminal SARAH domain found in the mammalian STE20-like protein kinase (MST) subfamily; The MST subfamily includes MST1 and MST2, as well as Drosophila melanogaster homolog protein, Hippo (Hpo). 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. 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 plays a key role in the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. This model corresponds to the C-terminal SARAH (Salvador-RassF-Hippo) domain of mammalian STE20-like protein kinases and the Drosophila melanogaster homolog Hippo.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 119617542 194 SLPELQNFLRILDKEEDEQLQNLKRRYTAYRQKLEEAL 231
Cdd:cd21884    8 SYEELQERLALLDPEMEREIEELRKRYQAKRQPILDAI 45