RhoBTB protein is an atypical member of the Rho family of small GTPases; Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila, and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase domain, a proline rich region, a tandem of two BTB (Broad-Complex, Tramtrack, and Bric a brac) domains, and a C-terminal region of unknown function. RhoBTB proteins may act as docking points for multiple components participating in signal transduction cascades. RhoBTB genes appeared upregulated in some cancer cell lines, suggesting a participation of RhoBTB proteins in the pathogenesis of particular tumors. Note that the Dictyostelium RacA GTPase domain is more closely related to Rac proteins than to RhoBTB proteins, where RacA actually belongs. Thus, the Dictyostelium RacA is not included here. Most Rho proteins contain a lipid modification site at the C-terminus; however, RhoBTB is one of few Rho subfamilies that lack this feature.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  13 ETIKCVVVGDNAVGKTRLICARACNTTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDEVSISLRLWDTFGDHHKD 92
Cdd:cd01873    1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  93 RRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRYADLEAVNRARRPLARPIKRGDILPPE 172
Cdd:cd01873   81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 568968400 173 KGREVAKELGIPYYETSVFDQFGIKDVFDNAIRAA 207
Cdd:cd01873  161 TGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain superfamily; Proteins in this superfamily are characterized by the presence of a common protein-protein interaction motif of about 100 amino acids, known as the BTB/POZ domain. Members include transcription factors, oncogenic proteins, ion channel proteins, and potassium channel tetramerization domain (KCTD) proteins. They have been identified in poxviruses and many eukaryotes, and have diverse functions, such as transcriptional regulation, chromatin remodeling, protein degradation and cytoskeletal regulation. Many BTB/POZ proteins contain one or two additional domains, such as kelch repeats, zinc-finger domains, FYVE (Fab1, YOTB, Vac1, and EEA1) fingers, or ankyrin repeats, among others. These special additional domains or interaction partners provide unique characteristics and functions to BTB/POZ proteins. In ion channel proteins and KCTD proteins, the BTB/POZ domain is also called the tetramerization (T1) domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 248 CPSAGTSDAACLLDNPLCADVLFVLHDEEHIFAHRIYLATSSSKFYDLFLMECEESpcwgggageevpcrdfqgrtqslg 327
Cdd:cd18355    1 CPSKSRNEAGQLLDNPLCADVMFILQEQVHIFAHRIYLATSSSKFYDLFLMECEES------------------------ 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 328 saeegkegpqrtpqadpgassgqdlpeslalqmeasgseghaLSGWSKGFVSMHREVRVNPISKRVGPVTVVRLDPSMQS 407
Cdd:cd18355   57 ------------------------------------------LSSWSKGFYSMHKEMQVNPVSNRPCPMTVVKMDSSIQH 94

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 568968400 408 GPFRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNKEAFMN 459
Cdd:cd18355   95 GPFKTVLRFLYTGQLDEKEKDLMRLAQIAEILEVFDLRMMVENIMNKEAFMN 146

RhoBTB protein is an atypical member of the Rho family of small GTPases; Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila, and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase domain, a proline rich region, a tandem of two BTB (Broad-Complex, Tramtrack, and Bric a brac) domains, and a C-terminal region of unknown function. RhoBTB proteins may act as docking points for multiple components participating in signal transduction cascades. RhoBTB genes appeared upregulated in some cancer cell lines, suggesting a participation of RhoBTB proteins in the pathogenesis of particular tumors. Note that the Dictyostelium RacA GTPase domain is more closely related to Rac proteins than to RhoBTB proteins, where RacA actually belongs. Thus, the Dictyostelium RacA is not included here. Most Rho proteins contain a lipid modification site at the C-terminus; however, RhoBTB is one of few Rho subfamilies that lack this feature.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  13 ETIKCVVVGDNAVGKTRLICARACNTTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDEVSISLRLWDTFGDHHKD 92
Cdd:cd01873    1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  93 RRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRYADLEAVNRARRPLARPIKRGDILPPE 172
Cdd:cd01873   81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 568968400 173 KGREVAKELGIPYYETSVFDQFGIKDVFDNAIRAA 207
Cdd:cd01873  161 TGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing protein 1 (RhoBTB1); RhoBTB1 is an atypical Rho family small guanosine triphosphatase (GTPase) and is a member of the RhoBTB subfamily, which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. The carboxyl terminal extension that harbors two BTB domains is capable of assembling cullin 3-dependent ubiquitin ligase complexes. RhoBTB1 functions as a tumor suppressor that regulates the integrity of the Golgi complex through the methyltransferase METTL7B. It also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex. This model corresponds to the first BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 248 CPSAGTSDAACLLDNPLCADVLFVLHDEEHIFAHRIYLATSSSKFYDLFLMECEESpcwgggageevpcrdfqgrtqslg 327
Cdd:cd18355    1 CPSKSRNEAGQLLDNPLCADVMFILQEQVHIFAHRIYLATSSSKFYDLFLMECEES------------------------ 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 328 saeegkegpqrtpqadpgassgqdlpeslalqmeasgseghaLSGWSKGFVSMHREVRVNPISKRVGPVTVVRLDPSMQS 407
Cdd:cd18355   57 ------------------------------------------LSSWSKGFYSMHKEMQVNPVSNRPCPMTVVKMDSSIQH 94

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 568968400 408 GPFRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNKEAFMN 459
Cdd:cd18355   95 GPFKTVLRFLYTGQLDEKEKDLMRLAQIAEILEVFDLRMMVENIMNKEAFMN 146

Rho (Ras homology) subfamily of Ras-like small GTPases; Members of this subfamily of Ras-like small GTPases include Cdc42 and Rac, as well as Rho isoforms.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400    17 CVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDEVSISLRLWDTFG--DHHKDRR 94
Cdd:smart00174   1 LVVVGDGAVGKTCLLIVYTTNAFPEDY------VPTVF--ENYSADVEV--------DGKPVELGLWDTAGqeDYDRLRP 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400    95 FAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPEKG 174
Cdd:smart00174  65 LSYPDTDVFLICFSVDSPASFENVKEKWYPEVKHFCPNVPIILVGTKLDLR-NDKSTLEELSKKKQEPVT------YEQG 137

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 568968400   175 REVAKELG-IPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:smart00174 138 QALAKRIGaVKYLECSALTQEGVREVFEEAIRAAL 172

BTB/POZ domain; The BTB (for BR-C, ttk and bab) or POZ (for Pox virus and Zinc finger) domain is present near the N-terminus of a fraction of zinc finger (pfam00096) proteins and in proteins that contain the pfam01344 motif such as Kelch and a family of pox virus proteins. The BTB/POZ domain mediates homomeric dimerization and in some instances heteromeric dimerization. The structure of the dimerized PLZF BTB/POZ domain has been solved and consists of a tightly intertwined homodimer. The central scaffolding of the protein is made up of a cluster of alpha-helices flanked by short beta-sheets at both the top and bottom of the molecule. POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  475 KECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLYTKQLSPNLDLD 554
Cdd:pfam00651   2 NELREQGELCDVTLVVGDKEFRAHKAVLAACSPYFKALFSGQESESSVSEITLDDVSPEDFEALLEFMYTGKLISEENVD 81

                          90       100
                  ....*....|....*....|....*.
gi 568968400  555 plELIALANRFCLTHLVALVEQHAVQ 580
Cdd:pfam00651  82 --DLLAAADKLQIPSLVDKCEEFLIK 105

small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this model include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.This model recognizes a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400   14 TIKCVVVGDNAVGKtrlicaracnTTLTqYQLLATHVptvwAIDQYR--VCQEVLERSrDVVDEVSISLRLWDTFG--DH 89
Cdd:TIGR00231   1 DIKIVIVGHPNVGK----------STLL-NSLLGNKG----SITEYYpgTTRNYVTTV-IEEDGKTYKFNLLDTAGqeDY 64

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400   90 HKDRRFAYGRSDVVVLCFSIANP-NSLNHVKTMWYQEIKHFCPR-TPVVLVGCQLDLRYADleavnrarrplarpikrgd 167
Cdd:TIGR00231  65 DAIRRLYYPQVERSLRVFDIVILvLDVEEILEKQTKEIIHHADSgVPIILVGNKIDLKDAD------------------- 125

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 568968400  168 iLPPEKGREVAKELGIPYYETSVFDQFGIKDVFDN 202
Cdd:TIGR00231 126 -LKTHVASEFAKLNGEPIIPLSAETGKNIDSAFKI 159

Broad-Complex, Tramtrack and Bric a brac; Domain in Broad-Complex, Tramtrack and Bric a brac. Also known as POZ (poxvirus and zinc finger) domain. Known to be a protein-protein interaction motif found at the N-termini of several C2H2-type transcription factors as well as Shaw-type potassium channels. Known structure reveals a tightly intertwined dimer formed via interactions between N-terminal strand and helix structures. However in a subset of BTB/POZ domains, these two secondary structures appear to be missing. Be aware SMART predicts BTB/POZ domains without the beta1- and alpha1-secondary structures.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 568968400   410 FRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNK 454
Cdd:smart00225  51 FRALLNFLYTGKLDLPEENVEELLELADYLQIPGLVELCEEFLLK 95

RhoBTB protein is an atypical member of the Rho family of small GTPases; Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila, and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase domain, a proline rich region, a tandem of two BTB (Broad-Complex, Tramtrack, and Bric a brac) domains, and a C-terminal region of unknown function. RhoBTB proteins may act as docking points for multiple components participating in signal transduction cascades. RhoBTB genes appeared upregulated in some cancer cell lines, suggesting a participation of RhoBTB proteins in the pathogenesis of particular tumors. Note that the Dictyostelium RacA GTPase domain is more closely related to Rac proteins than to RhoBTB proteins, where RacA actually belongs. Thus, the Dictyostelium RacA is not included here. Most Rho proteins contain a lipid modification site at the C-terminus; however, RhoBTB is one of few Rho subfamilies that lack this feature.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  13 ETIKCVVVGDNAVGKTRLICARACNTTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDEVSISLRLWDTFGDHHKD 92
Cdd:cd01873    1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  93 RRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRYADLEAVNRARRPLARPIKRGDILPPE 172
Cdd:cd01873   81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 568968400 173 KGREVAKELGIPYYETSVFDQFGIKDVFDNAIRAA 207
Cdd:cd01873  161 TGRAVAKELGIPYYETSVVTQFGVKDVFDNAIRAA 195

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing protein 1 (RhoBTB1); RhoBTB1 is an atypical Rho family small guanosine triphosphatase (GTPase) and is a member of the RhoBTB subfamily, which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. The carboxyl terminal extension that harbors two BTB domains is capable of assembling cullin 3-dependent ubiquitin ligase complexes. RhoBTB1 functions as a tumor suppressor that regulates the integrity of the Golgi complex through the methyltransferase METTL7B. It also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex. This model corresponds to the first BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 248 CPSAGTSDAACLLDNPLCADVLFVLHDEEHIFAHRIYLATSSSKFYDLFLMECEESpcwgggageevpcrdfqgrtqslg 327
Cdd:cd18355    1 CPSKSRNEAGQLLDNPLCADVMFILQEQVHIFAHRIYLATSSSKFYDLFLMECEES------------------------ 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 328 saeegkegpqrtpqadpgassgqdlpeslalqmeasgseghaLSGWSKGFVSMHREVRVNPISKRVGPVTVVRLDPSMQS 407
Cdd:cd18355   57 ------------------------------------------LSSWSKGFYSMHKEMQVNPVSNRPCPMTVVKMDSSIQH 94

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 568968400 408 GPFRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNKEAFMN 459
Cdd:cd18355   95 GPFKTVLRFLYTGQLDEKEKDLMRLAQIAEILEVFDLRMMVENIMNKEAFMN 146

second BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing protein 2 (RhoBTB2); RhoBTB2, also called Deleted in breast cancer 2 gene protein (DBC2) or p83, is an atypical Rho family small guanosine triphosphatase (GTPase) and is a member of the RhoBTB subfamily, which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. The carboxyl terminal extension that harbors two BTB domains is capable of assembling cullin 3-dependent ubiquitin ligase complexes. RhoBTB2 functions as a tumor suppressor that regulates the expression of the methyltransferase METTL7A. It also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex. This model corresponds to the second BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 464 KAFHVRKANRIKECLSKGTFSDVTFTLDDGAISAHKPLLICSCEWMAAMFGGSFVESANREVHLPNINKMSMQAVLEYLY 543
Cdd:cd18359    1 KAFHVRRTNRVKECLAKGTFSDVTFMLDDGTISAHKPLLISSCDWMAAMFGGPFVESSTTEVVFPYTSRSSMRAVLEYLY 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 568968400 544 TKQLSPNLDLDPLELIALANRFCLTHLVALVEQHAVQELTKAA 586
Cdd:cd18359   81 TGQFSSSPDLDDMKLIILANRLCLPHLVALTEQYTVTVLMEAA 123

BACK (BTB and C-terminal Kelch) domain found in Rho-related BTB domain-containing protein 2 (RhoBTB2); RhoBTB2, also called Deleted in breast cancer 2 gene protein (DBC2), or p83, is an atypical member of the Rho GTPase family of signaling proteins, which is characterized by containing a carboxyl terminal extension that harbors two BTB domains and a BACK domain and is capable of assembling cullin 3-dependent ubiquitin ligase complexes. It functions as a tumor suppressor that regulates the expression of the methyltransferase METTL7A. RhoBTB2 also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 592 IDGEVLSYLELAQFHNANQLAAWCLHHICTNYNSVCSKFRKEIKSKSADNQEYFERHRWPPVWYLKEEDHYQRVKREREK 671
Cdd:cd18531    1 IDGQVLVYLELAQFHNAKQLADWCLHHICTNYNSVCRKFPRDMKAMSPENQEHFEKHRWPPVWYLKEEDRYLRSKKEREK 80

                         90
                 ....*....|....*..
gi 568968400 672 EDLALNKHHSRRKWCFW 688
Cdd:cd18531   81 EEELLRKQHPKRKWCFW 97

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing protein 2 (RhoBTB2); RhoBTB2, also called Deleted in breast cancer 2 gene protein (DBC2) or p83, is an atypical Rho family small guanosine triphosphatase (GTPase) and is a member of the RhoBTB subfamily, which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. The carboxyl terminal extension that harbors two BTB domains is capable of assembling cullin 3-dependent ubiquitin ligase complexes. RhoBTB2 functions as a tumor suppressor that regulates the expression of the methyltransferase METTL7A. It also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex. This model corresponds to the first BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 246 PECPSAGTSDAACLLDNPLCADVLFVLHDEEHIFAHRIYLATSSSKFYDLFLMECeespcwgggageevpcrdfqgrtqs 325
Cdd:cd18356    1 PDPPTKSEEHPAHLLEDPLCADVILVLQERIRIYAHKIYLSTSSSKFYDLFLMDR------------------------- 55

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 326 lgsaeegkegpqrtpqadpgassgqdlpeslalqmeasgseGHALSGWSKGFVSMHREVRVNPISKRVGPVTVVRLDPSM 405
Cdd:cd18356   56 -----------------------------------------GRDLSSWSRAFVSIQEEVAEDPLTYKSRLMVVVKMDSSI 94

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568968400 406 QSGPFRTLLRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMNKEAFMN 459
Cdd:cd18356   95 QPGPFRAVLKYLYTGELDENERDLMHIAHIAELLEVFDLRMMVANILNNEAFMN 148

Ras homology family 4 (Rho4) of small guanosine triphosphatases (GTPases)-like; Rho4 is a GTPase that controls septum degradation by regulating secretion of Eng1 or Agn1 during cytokinesis. Rho4 also plays a role in cell morphogenesis. Rho4 regulates septation and cell morphology by controlling the actin cytoskeleton and cytoplasmic microtubules. The localization of Rho4 is modulated by Rdi1, which may function as a GDI, and by Rga9, which is believed to function as a GAP. In S. pombe, both Rho4 deletion and Rho4 overexpression result in a defective cell wall, suggesting a role for Rho4 in maintaining cell wall integrity. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  15 IKCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVwaIDQYRvcqevlersRDVVDEVS--ISLRLWDTFG--DHH 90
Cdd:cd04132    4 VKIVVVGDGGCGKTCLLMVYAQGSFPEEY------VPTV--FENYV---------TTLQVPNGkiIELALWDTAGqeDYD 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  91 KDRRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilp 170
Cdd:cd04132   67 RLRPLSYPDVDVILICYSVDNPTSLDNVEDKWYPEVNHFCPGTPIVLVGLKTDLR-KDKNSVSKLRAQGLEPVT------ 139

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568968400 171 PEKGREVAKELG-IPYYETSVFDQFGIKDVFDNAIRAALiSRRHLQFWKSHLKK 223
Cdd:cd04132  140 PEQGESVAKSIGaVAYIECSAKLMENVDEVFDAAINVAL-SKSGRAARKKKKKK 192

Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)-like consists of Rac1, Rac2 and Rac3; The Rac1-like subfamily consists of Rac1, Rac2, and Rac3 proteins, plus the splice variant Rac1b that contains a 19-residue insertion near switch II relative to Rac1. While Rac1 is ubiquitously expressed, Rac2 and Rac3 are largely restricted to hematopoietic and neural tissues respectively. Rac1 stimulates the formation of actin lamellipodia and membrane ruffles. It also plays a role in cell-matrix adhesion and cell anoikis. In intestinal epithelial cells, Rac1 is an important regulator of migration and mediates apoptosis. Rac1 is also essential for RhoA-regulated actin stress fiber and focal adhesion complex formation. In leukocytes, Rac1 and Rac2 have distinct roles in regulating cell morphology, migration, and invasion, but are not essential for macrophage migration or chemotaxis. Rac3 has biochemical properties that are closely related to Rac1, such as effector interaction, nucleotide binding, and hydrolysis; Rac2 has a slower nucleotide association and is more efficiently activated by the RacGEF Tiam1. Both Rac1 and Rac3 have been implicated in the regulation of cell migration and invasion in human metastatic breast cancer. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  15 IKCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYrvcqevlerSRDV-VDEVSISLRLWDTFG--DHHK 91
Cdd:cd01871    2 IKCVVVGDGAVGKTCLLISYTTNAFPGEY------IPTVF--DNY---------SANVmVDGKPVNLGLWDTAGqeDYDR 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  92 DRRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKRgdilpp 171
Cdd:cd01871   65 LRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLR-DDKDTIEKLKEKKLTPITY------ 137

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 568968400 172 EKGREVAKELG-IPYYETSVFDQFGIKDVFDNAIRA 206
Cdd:cd01871  138 PQGLAMAKEIGaVKYLECSALTQRGLKTVFDEAIRA 173

cell division cycle 42 (Cdc42) is a small GTPase of the Rho family; Cdc42 is an essential GTPase that belongs to the Rho family of Ras-like GTPases. These proteins act as molecular switches by responding to exogenous and/or endogenous signals and relaying those signals to activate downstream components of a biological pathway. Cdc42 transduces signals to the actin cytoskeleton to initiate and maintain polarized growth and to mitogen-activated protein morphogenesis. In the budding yeast Saccharomyces cerevisiae, Cdc42 plays an important role in multiple actin-dependent morphogenetic events such as bud emergence, mating-projection formation, and pseudohyphal growth. In mammalian cells, Cdc42 regulates a variety of actin-dependent events and induces the JNK/SAPK protein kinase cascade, which leads to the activation of transcription factors within the nucleus. Cdc42 mediates these processes through interactions with a myriad of downstream effectors, whose number and regulation we are just starting to understand. In addition, Cdc42 has been implicated in a number of human diseases through interactions with its regulators and downstream effectors. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  14 TIKCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRVCQevlersrdVVDEVSISLRLWDTFG--DHHK 91
Cdd:cd01874    1 TIKCVVVGDGAVGKTCLLISYTTNKFPSEY------VPTVF--DNYAVTV--------MIGGEPYTLGLFDTAGqeDYDR 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  92 DRRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilpP 171
Cdd:cd01874   65 LRPLSYPQTDVFLVCFSVVSPSSFENVKEKWVPEITHHCPKTPFLLVGTQIDLR-DDPSTIEKLAKNKQKPIT------P 137

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 568968400 172 EKGREVAKELG-IPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:cd01874  138 ETGEKLARDLKaVKYVECSALTQKGLKNVFDEAILAAL 175

Ras homology family A (RhoA)-like includes RhoA, RhoB and RhoC; The RhoA subfamily consists of RhoA, RhoB, and RhoC. RhoA promotes the formation of stress fibers and focal adhesions, regulating cell shape, attachment, and motility. RhoA can bind to multiple effector proteins, thereby triggering different downstream responses. In many cell types, RhoA mediates local assembly of the contractile ring, which is necessary for cytokinesis. RhoA is vital for muscle contraction; in vascular smooth muscle cells, RhoA plays a key role in cell contraction, differentiation, migration, and proliferation. RhoA activities appear to be elaborately regulated in a time- and space-dependent manner to control cytoskeletal changes. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. RhoA and RhoC are observed only in geranylgeranylated forms; however, RhoB can be present in palmitoylated, farnesylated, and geranylgeranylated forms. RhoA and RhoC are highly relevant for tumor progression and invasiveness; however, RhoB has recently been suggested to be a tumor suppressor. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  16 KCVVVGDNAVGKTRLIcaracnTTLTQYQLLATHVPTVWaiDQYrvcqevlerSRDV-VDEVSISLRLWDTFG--DHHKD 92
Cdd:cd01870    3 KLVIVGDGACGKTCLL------IVFSKDQFPEVYVPTVF--ENY---------VADIeVDGKQVELALWDTAGqeDYDRL 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  93 RRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKrgdilpPE 172
Cdd:cd01870   66 RPLSYPDTDVILMCFSIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLR-NDEHTIRELAKMKQEPVK------PE 138

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 568968400 173 KGREVAKELG-IPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:cd01870  139 EGRAMAEKIGaFGYLECSAKTKEGVREVFEMATRAAL 175

Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See pfam00009 pfam00025, pfam00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400   16 KCVVVGDNAVGKTRLICaracntTLTQYQLLATHVPTVwAIDQYRvcqevlersRDV-VDEVSISLRLWDTFG--DHHKD 92
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLI------RFTQNKFPEEYIPTI-GVDFYT---------KTIeVDGKTVKLQIWDTAGqeRFRAL 64

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400   93 RRFAYGRSDVVVLCFSIANPNSLNHVKTmWYQEIKHFCP-RTPVVLVGCQLDLRyaDLEAVnrarrplarpikrgdilPP 171
Cdd:pfam00071  65 RPLYYRGADGFLLVYDITSRDSFENVKK-WVEEILRHADeNVPIVLVGNKCDLE--DQRVV-----------------ST 124

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 568968400  172 EKGREVAKELGIPYYETSVFDQFGIKDVFDNAIRAAL 208
Cdd:pfam00071 125 EEGEALAKELGLPFMETSAKTNENVEEAFEELAREIL 161

first BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Rho-related BTB domain-containing proteins (RhoBTB); RhoBTB proteins constitute a subfamily of atypical members within the Rho family of small guanosine triphosphatases (GTPases), which is characterized by containing a GTPase domain (in most cases, non-functional) followed by a proline-rich region, tandem BTB domains, and a conserved C-terminal region. In vertebrates, the RhoBTB subfamily consists of 3 isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. Orthologs are present in several other eukaryotes, such as Drosophila and Dictyostelium, but have been lost in plants and fungi. This model corresponds to the first BTB domain. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 254 SDAACLLDNPLCADVLFVLHDEEHIFAHRIYLATSSSKFYDLFLMEceespcwgggageevpcrdfqgrtqslgsaeegk 333
Cdd:cd18299    1 EDLRNLLHSPSCADVVFILQGGVRIFAHRIVLAAASSVFADLFLMM---------------------------------- 46

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400 334 egpqrtpqadpgassgqdlpeslalqmeasgseghalsgwskgfvsmhrevrvnpiskrvgpvTVVRLDPSMQSGPFRTL 413
Cdd:cd18299   47 ---------------------------------------------------------------TVVTLDSDITPEAFRRV 63

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568968400 414 LRFLYSGQLDEKEKDLLGLAQMAEVLEMFDLRMMVENIMN 453
Cdd:cd18299   64 LEFLYTGVLDENEDDLKELKDAAELLELFDLVMMCTNVLN 103

Rho-related protein from plants (Rop)-like; The Rop (Rho-related protein from plants) subfamily plays a role in diverse cellular processes, including cytoskeletal organization, pollen and vegetative cell growth, hormone responses, stress responses, and pathogen resistance. Rops are able to regulate several downstream pathways to amplify a specific signal by acting as master switches early in the signaling cascade. They transmit a variety of extracellular and intracellular signals. Rops are involved in establishing cell polarity in root-hair development, root-hair elongation, pollen-tube growth, cell-shape formation, responses to hormones such as abscisic acid (ABA) and auxin, responses to abiotic stresses such as oxygen deprivation, and disease resistance and disease susceptibility. An individual Rop can have a unique function or an overlapping function shared with other Rop proteins; in addition, a given Rop-regulated function can be controlled by one or multiple Rop proteins. For example, Rop1, Rop3, and Rop5 are all involved in pollen-tube growth; Rop2 plays a role in response to low-oxygen environments, cell-morphology, and root-hair development; root-hair development is also regulated by Rop4 and Rop6; Rop6 is also responsible for ABA response, and ABA response is also regulated by Rop10. Plants retain some of the regulatory mechanisms that are shared by other members of the Rho family, but have also developed a number of unique modes for regulating Rops. Unique RhoGEFs have been identified that are exclusively active toward Rop proteins, such as those containing the domain PRONE (plant-specific Rop nucleotide exchanger). Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  15 IKCVVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRvcqevlerSRDVVDEVSISLRLWDTFG--DHHKD 92
Cdd:cd04133    2 IKCVTVGDGAVGKTCMLISYTSNTFPTDY------VPTVF--DNFS--------ANVVVDGNTVNLGLWDTAGqeDYNRL 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  93 RRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLR-----YADleavnrarRPLARPIKRGd 167
Cdd:cd04133   66 RPLSYRGADVFLLAFSLISKASYENVLKKWIPELRHYAPGVPIVLVGTKLDLRddkqfFAD--------HPGAVPITTA- 136

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 568968400 168 ilppeKGREVAKELGIPYY-ETSVFDQFGIKDVFDNAIRAAL 208
Cdd:cd04133  137 -----QGEELRKQIGAAAYiECSSKTQQNVKAVFDAAIKVVL 173

Rnd3/RhoE/Rho8 GTPases; Rnd3/RhoE/Rho8 subfamily. Rnd3/RhoE/Rho8 is a member of the novel Rho subfamily Rnd, together with Rnd1/Rho6 and Rnd2/Rho7. Rnd3/RhoE is known to bind the serine-threonine kinase ROCK I. Unphosphorylated Rnd3/RhoE associates primarily with membranes, but ROCK I-phosphorylated Rnd3/RhoE localizes in the cytosol. Phosphorylation of Rnd3/RhoE correlates with its activity in disrupting RhoA-induced stress fibers and inhibiting Ras-induced fibroblast transformation. In cells that lack stress fibers, such as macrophages and monocytes, Rnd3/RhoE induces a redistribution of actin, causing morphological changes in the cell. In addition, Rnd3/RhoE has been shown to inhibit cell cycle progression in G1 phase at a point upstream of the pRb family pocket protein checkpoint. Rnd3/RhoE has also been shown to inhibit Ras- and Raf-induced fibroblast transformation. In mammary epithelial tumor cells, Rnd3/RhoE regulates the assembly of the apical junction complex and tight junction formation. Rnd3/RhoE is underexpressed in prostate cancer cells both in vitro and in vivo; re-expression of Rnd3/RhoE suppresses cell cycle progression and increases apoptosis, suggesting it may play a role in tumor suppression. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  13 ETIKC--VVVGDNAVGKTRLICARACNTTLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDEVSISLRLWDTFGDHH 90
Cdd:cd04172    2 QNVKCkiVVVGDSQCGKTALLHVFAKDCFPENY------VPTVF--ENYTASFEI--------DTQRIELSLWDTSGSPY 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  91 KD--RRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIKRgdi 168
Cdd:cd04172   66 YDnvRPLSYPDSDAVLICFDISRPETLDSVLKKWKGEIQEFCPNTKMLLVGCKSDLR-TDVSTLVELSNHRQTPVSY--- 141

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 568968400 169 lppEKGREVAKELG-IPYYETSVF-DQFGIKDVFDNAIRAAL 208
Cdd:cd04172  142 ---DQGANMAKQIGaATYIECSALqSENSVRDIFHVATLACV 180

Rnd1/Rho6 GTPases; Rnd1/Rho6 is a member of the novel Rho subfamily Rnd, together with Rnd2/Rho7 and Rnd3/RhoE/Rho8. Rnd1/Rho6 binds GTP but does not hydrolyze it to GDP, indicating that it is constitutively active. In rat, Rnd1/Rho6 is highly expressed in the cerebral cortex and hippocampus during synapse formation, and plays a role in spine formation. Rnd1/Rho6 is also expressed in the liver and in endothelial cells, and is upregulated in uterine myometrial cells during pregnancy. Like Rnd3/RhoE/Rho8, Rnd1/Rho6 is believed to function as an antagonist to RhoA. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400   9 RPNVETIKCVVVGDNAVGKTRL--ICARACNTTltqyqllaTHVPTVWaiDQYRVCQEVlersrdvvDEVSISLRLWDTF 86
Cdd:cd04174    8 QPLVVRCKLVLVGDVQCGKTAMlqVLAKDCYPE--------TYVPTVF--ENYTACLET--------EEQRVELSLWDTS 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568968400  87 GDHHKD--RRFAYGRSDVVVLCFSIANPNSLNHVKTMWYQEIKHFCPRTPVVLVGCQLDLRyADLEAVNRARRPLARPIK 164
Cdd:cd04174   70 GSPYYDnvRPLCYSDSDAVLLCFDISRPEIFDSALKKWRAEILDYCPSTRILLIGCKTDLR-TDLSTLMELSNQKQAPIS 148

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568968400 165 RgdilppEKGREVAKELGIP-YYETSVF-DQFGIKDVFDNAiRAALISRRHLQFWKSHLKKVQKPLLQ 230
Cdd:cd04174  149 Y------EQGCAMAKQLGAEaYLECSAFtSEKSIHSIFRTA-SLLCINKLSPLAKKSPVRSLSKRLLH 209