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 1907101313  35 ETIKCVVVGDNAVGKTRLICARACNATLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDDVSVSLRLWDTFGDHHKD 114
Cdd:cd01873     1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 115 RRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRYADLEAVNRARRPLARPIKPNEILPPE 194
Cdd:cd01873    81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPE 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1907101313 195 KGREVAKELGIPYYETSVVAQFGIKDVFDNAIRAA 229
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 1907101313 272 SSSEECPAHLLEDPLCADVILVLQERVRIFAHKIYLSTSSSKFYDLFLMDlsegelggpsgsggprpedhrshpeqhhhh 351
Cdd:cd18356     5 TKSEEHPAHLLEDPLCADVILVLQERIRIYAHKIYLSTSSSKFYDLFLMD------------------------------ 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 352 hhhhhgrdfllraasfdvcesvdeaggsgpaglrastsdgilrgngtgylpgRGRVLSSWSRAFVSIQEEMAEDPLTFKS 431
Cdd:cd18356    55 ----------------------------------------------------RGRDLSSWSRAFVSIQEEVAEDPLTYKS 82

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907101313 432 RLMVVVKMDNSIQPGPFRAVLKYLYTGELGENERDLMHIAHIAELLEVFDLRMMVANILNNEAFMN 497
Cdd:cd18356    83 RLMVVVKMDSSIQPGPFRAVLKYLYTGELDENERDLMHIAHIAELLEVFDLRMMVANILNNEAFMN 148

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 1907101313  35 ETIKCVVVGDNAVGKTRLICARACNATLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDDVSVSLRLWDTFGDHHKD 114
Cdd:cd01873     1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 115 RRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRYADLEAVNRARRPLARPIKPNEILPPE 194
Cdd:cd01873    81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPE 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1907101313 195 KGREVAKELGIPYYETSVVAQFGIKDVFDNAIRAA 229
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 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 1907101313 272 SSSEECPAHLLEDPLCADVILVLQERVRIFAHKIYLSTSSSKFYDLFLMDlsegelggpsgsggprpedhrshpeqhhhh 351
Cdd:cd18356     5 TKSEEHPAHLLEDPLCADVILVLQERIRIYAHKIYLSTSSSKFYDLFLMD------------------------------ 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 352 hhhhhgrdfllraasfdvcesvdeaggsgpaglrastsdgilrgngtgylpgRGRVLSSWSRAFVSIQEEMAEDPLTFKS 431
Cdd:cd18356    55 ----------------------------------------------------RGRDLSSWSRAFVSIQEEVAEDPLTYKS 82

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907101313 432 RLMVVVKMDNSIQPGPFRAVLKYLYTGELGENERDLMHIAHIAELLEVFDLRMMVANILNNEAFMN 497
Cdd:cd18356    83 RLMVVVKMDSSIQPGPFRAVLKYLYTGELDENERDLMHIAHIAELLEVFDLRMMVANILNNEAFMN 148

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 1907101313   39 CVVVGDNAVGKTRLICARACNATLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDDVSVSLRLWDTFG--DHHKDRR 116
Cdd:smart00174   1 LVVVGDGAVGKTCLLIVYTTNAFPEDY------VPTVF--ENYSADVEV--------DGKPVELGLWDTAGqeDYDRLRP 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313  117 FAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRyADLEAVNRARRPLARPIKpneilpPEKG 196
Cdd:smart00174  65 LSYPDTDVFLICFSVDSPASFENVKEKWYPEVKHFCPNVPIILVGTKLDLR-NDKSTLEELSKKKQEPVT------YEQG 137

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1907101313  197 REVAKELG-IPYYETSVVAQFGIKDVFDNAIRAAL 230
Cdd:smart00174 138 QALAKRIGaVKYLECSALTQEGVREVFEEAIRAAL 172

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        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313  523 DVTFILDDGTISAHKPLLISSCDWMAAMFGGPFVESSTREVVFPYTSKSCMRAVLEYLYTGMFTSSPDlDDMKLIVLANR 602
Cdd:smart00225   1 DVTLVVGGKKFHAHKAVLAAHSPYFKALFSSDFKESDKSEIYLDDVSPEDFRALLNFLYTGKLDLPEE-NVEELLELADY 79

                           90
                   ....*....|...
gi 1907101313  603 LCLPHLVALTEQY 615
Cdd:smart00225  80 LQIPGLVELCEEF 92

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 1907101313  36 TIKCVVVGDNAVGKTrlicaracnaTLTqYQLLATHVptvwAIDQYR--VCQEVLERSrDVVDDVSVSLRLWDTFG--DH 111
Cdd:TIGR00231   1 DIKIVIVGHPNVGKS----------TLL-NSLLGNKG----SITEYYpgTTRNYVTTV-IEEDGKTYKFNLLDTAGqeDY 64

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 112 HKDRRFAYGRSDVVVLCFSIANP-NSLHHVKTMWYPEIKHFCPR-APVILVGCQLDLRYADleavnrarrplarpikpne 189
Cdd:TIGR00231  65 DAIRRLYYPQVERSLRVFDIVILvLDVEEILEKQTKEIIHHADSgVPIILVGNKIDLKDAD------------------- 125

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1907101313 190 iLPPEKGREVAKELGIPYYETSVVAQFGIKDVFDN 224
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        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313  407 VLSSWSRAFVSIQEEmaedplTFKSRLMVVVKMDNsIQPGPFRAVLKYLYTGELGENERDLMHIAHIAELLEVFDLRMMV 486
Cdd:smart00225  17 VLAAHSPYFKALFSS------DFKESDKSEIYLDD-VSPEDFRALLNFLYTGKLDLPEENVEELLELADYLQIPGLVELC 89

                   ....*.
gi 1907101313  487 ANILNN 492
Cdd:smart00225  90 EEFLLK 95

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
                  ....*....|....*....|....*....|....*.
gi 1907101313 289 DVILVLQERvRIFAHKIYLSTSSSKFYDLFLMDLSE 324
Cdd:pfam00651  12 DVTLVVGDK-EFRAHKAVLAACSPYFKALFSGQESE 46

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 1907101313  35 ETIKCVVVGDNAVGKTRLICARACNATLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDDVSVSLRLWDTFGDHHKD 114
Cdd:cd01873     1 ETIKCVVVGDNAVGKTRLICARACNKTLTQYQLLATHVPTVWAIDQYRVCQEVLERSRDVVDGVSVSLRLWDTFGDHDKD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 115 RRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRYADLEAVNRARRPLARPIKPNEILPPE 194
Cdd:cd01873    81 RRFAYGRSDVVLLCFSIASPNSLRNVKTMWYPEIRHFCPRVPVILVGCKLDLRYADLDEVNRARRPLARPIKNADILPPE 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1907101313 195 KGREVAKELGIPYYETSVVAQFGIKDVFDNAIRAA 229
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 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 1907101313 272 SSSEECPAHLLEDPLCADVILVLQERVRIFAHKIYLSTSSSKFYDLFLMDlsegelggpsgsggprpedhrshpeqhhhh 351
Cdd:cd18356     5 TKSEEHPAHLLEDPLCADVILVLQERIRIYAHKIYLSTSSSKFYDLFLMD------------------------------ 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 352 hhhhhgrdfllraasfdvcesvdeaggsgpaglrastsdgilrgngtgylpgRGRVLSSWSRAFVSIQEEMAEDPLTFKS 431
Cdd:cd18356    55 ----------------------------------------------------RGRDLSSWSRAFVSIQEEVAEDPLTYKS 82

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907101313 432 RLMVVVKMDNSIQPGPFRAVLKYLYTGELGENERDLMHIAHIAELLEVFDLRMMVANILNNEAFMN 497
Cdd:cd18356    83 RLMVVVKMDSSIQPGPFRAVLKYLYTGELDENERDLMHIAHIAELLEVFDLRMMVANILNNEAFMN 148

Ras homology family (Rho) of small guanosine triphosphatases (GTPases); Members of the Rho (Ras homology) family include RhoA, Cdc42, Rac, Rnd, Wrch1, RhoBTB, and Rop. There are 22 human Rho family members identified currently. These proteins are all involved in the reorganization of the actin cytoskeleton in response to external stimuli. They also have roles in cell transformation by Ras in cytokinesis, in focal adhesion formation and in the stimulation of stress-activated kinase. These various functions are controlled through distinct effector proteins and mediated through a GTP-binding/GTPase cycle involving three classes of regulating proteins: GAPs (GTPase-activating proteins), GEFs (guanine nucleotide exchange factors), and GDIs (guanine nucleotide dissociation inhibitors). 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. Since crystal structures often lack C-terminal residues, this feature is not available for annotation in many of the CDs in the hierarchy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313  37 IKCVVVGDNAVGKTRLICARACNATLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDDVSVSLRLWDTFGDHHKD-- 114
Cdd:cd00157     1 IKIVVVGDGAVGKTCLLISYTTNKFPTEY------VPTVF--DNYSANVTV--------DGKQVNLGLWDTAGQEEYDrl 64

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 115 RRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRYADLeavnrarrPLARPIKPNEILPPE 194
Cdd:cd00157    65 RPLSYPQTDVFLLCFSVDSPSSFENVKTKWYPEIKHYCPNVPIILVGTKIDLRDDGN--------TLKKLEKKQKPITPE 136

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1907101313 195 KGREVAKELG-IPYYETSVVAQFGIKDVFDNAIRA 228
Cdd:cd00157   137 EGEKLAKEIGaVKYMECSALTQEGLKEVFDEAIRA 171

BACK (BTB and C-terminal Kelch) domain found in Rho-related BTB domain-containing protein 1 (RhoBTB1); RhoBTB1 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 integrity of the Golgi complex through the methyltransferase METTL7B. RhoBTB1 also acts an adaptor of the Cullin-3-dependent E3 ubiquitin ligase complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 630 IDGDVLVFLELAQFHCAYQLADWCLHHICTNYNNVCRKFPRDMKAMSPENQEYFEKHRWPPVWYLKEEDHYQRARKEREK 709
Cdd:cd18530     1 IDGEVLTYLELAQFHNAHQLAAWCLHHICTNYNSVCSKFRKEIKSKSPENQEYFERHRWPPVWYLKEEDHYQRVKKEREK 80

                          90
                  ....*....|....*...
gi 1907101313 710 EDYLHLRRQPKRRWLFWN 727
Cdd:cd18530    81 EDVALHKHHSKRKWCFWN 98

second 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, a tandem of 2 BTB domains, and a conserved C-terminal region. In humans, 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 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 1907101313 513 KECLAKGTFSDVTFILDDGTISAHKPLLISSCDWMAAMFGGPFVESSTREVVFPYTSKSCMRAVLEYLYTGMFTSSPDLD 592
Cdd:cd18300     1 KLFLNKGLFSDVTFIVEDGTIPAHKALLVARCDVMAAMFGGNFRESSAKEVELPGVSKETFLALLEYLYTDQAPILEDGD 80

                          90       100
                  ....*....|....*....|....*...
gi 1907101313 593 DMKLIVLANRLCLPHLVALTEQYTVTGL 620
Cdd:cd18300    81 CVGLIVLANRLCLPRLVALCEQYIVKEL 108

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 1907101313  37 IKCVVVGDNAVGKTRLICARACNATLTQYqllathVPTVwaIDQYRvcqevlersRDVVDDVS--VSLRLWDTFG--DHH 112
Cdd:cd04132     4 VKIVVVGDGGCGKTCLLMVYAQGSFPEEY------VPTV--FENYV---------TTLQVPNGkiIELALWDTAGqeDYD 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 113 KDRRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRyADLEAVNRARRPLARPIKpneilp 192
Cdd:cd04132    67 RLRPLSYPDVDVILICYSVDNPTSLDNVEDKWYPEVNHFCPGTPIVLVGLKTDLR-KDKNSVSKLRAQGLEPVT------ 139

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907101313 193 PEKGREVAKELG-IPYYETSVVAQFGIKDVFDNAIRAALiSRRHLQFWKS 241
Cdd:cd04132   140 PEQGESVAKSIGaVAYIECSAKLMENVDEVFDAAINVAL-SKSGRAARKK 188

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 1907101313  37 IKCVVVGDNAVGKTRLICARACNATLTQYqllathVPTVWaiDQYrvcqevlerSRDV-VDDVSVSLRLWDTFG--DHHK 113
Cdd:cd01871     2 IKCVVVGDGAVGKTCLLISYTTNAFPGEY------IPTVF--DNY---------SANVmVDGKPVNLGLWDTAGqeDYDR 64

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 114 DRRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRyADLEAVNRARRPLARPIKpneilpP 193
Cdd:cd01871    65 LRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLR-DDKDTIEKLKEKKLTPIT------Y 137

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1907101313 194 EKGREVAKELG-IPYYETSVVAQFGIKDVFDNAIRA 228
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 1907101313  36 TIKCVVVGDNAVGKTRLICARACNATLTQYqllathVPTVWaiDQYRVCQevlersrdVVDDVSVSLRLWDTFG--DHHK 113
Cdd:cd01874     1 TIKCVVVGDGAVGKTCLLISYTTNKFPSEY------VPTVF--DNYAVTV--------MIGGEPYTLGLFDTAGqeDYDR 64

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 114 DRRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRyADLEAVNRARRPLARPIKpneilpP 193
Cdd:cd01874    65 LRPLSYPQTDVFLVCFSVVSPSSFENVKEKWVPEITHHCPKTPFLLVGTQIDLR-DDPSTIEKLAKNKQKPIT------P 137

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1907101313 194 EKGREVAKELG-IPYYETSVVAQFGIKDVFDNAIRAAL 230
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 1907101313  38 KCVVVGDNAVGKTRLICaracnaTLTQYQLLATHVPTVWaiDQYrvcqevlerSRDV-VDDVSVSLRLWDTFG--DHHKD 114
Cdd:cd01870     3 KLVIVGDGACGKTCLLI------VFSKDQFPEVYVPTVF--ENY---------VADIeVDGKQVELALWDTAGqeDYDRL 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 115 RRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRyADLEAVNRARRPLARPIKpneilpPE 194
Cdd:cd01870    66 RPLSYPDTDVILMCFSIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKDLR-NDEHTIRELAKMKQEPVK------PE 138

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1907101313 195 KGREVAKELG-IPYYETSVVAQFGIKDVFDNAIRAAL 230
Cdd:cd01870   139 EGRAMAEKIGaFGYLECSAKTKEGVREVFEMATRAAL 175

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 1907101313 276 ECPAHLLEDPLCADVILVLQERVRIFAHKIYLSTSSSKFYDLFLMdlsegelggpsgsggprpedhrshpeqhhhhhhhh 355
Cdd:cd18299     1 EDLRNLLHSPSCADVVFILQGGVRIFAHRIVLAAASSVFADLFLM----------------------------------- 45

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 356 hgrdfllraasfdvcesvdeaggsgpaglrastsdgilrgngtgylpgrgrvlsswsrafvsiqeemaedpltfksrlMV 435
Cdd:cd18299    46 ------------------------------------------------------------------------------MT 47

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907101313 436 VVKMDNSIQPGPFRAVLKYLYTGELGENERDLMHIAHIAELLEVFDLRMMVANILN 491
Cdd:cd18299    48 VVTLDSDITPEAFRRVLEFLYTGVLDENEDDLKELKDAAELLELFDLVMMCTNVLN 103

Rho family GTPase subfamily Rnd includes Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8; The Rnd subfamily contains Rnd1/Rho6, Rnd2/Rho7, and Rnd3/RhoE/Rho8. These novel Rho family proteins have substantial structural differences compared to other Rho members, including N- and C-terminal extensions relative to other Rhos. Rnd3/RhoE is farnesylated at the C-terminal prenylation site, unlike most other Rho proteins that are geranylgeranylated. In addition, Rnd members are unable to hydrolyze GTP and are resistant to GAP activity. They are believed to exist only in the GTP-bound conformation, and are antagonists of RhoA activity. 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 1907101313  37 IKCVVVGDNAVGKTRLICARACNATLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDDVSVSLRLWDTFGDHHKD-- 114
Cdd:cd04131     2 CKIVLVGDSQCGKTALLQVFAKDSFPENY------VPTVF--ENYTASFEV--------DKQRIELSLWDTSGSPYYDnv 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 115 RRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRyADLEAVNRARRPLARPIKpneilpPE 194
Cdd:cd04131    66 RPLSYPDSDAVLICFDISRPETLDSVLKKWKGEVREFCPNTPVLLVGCKSDLR-TDLSTLTELSNKRQIPVS------HE 138

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1907101313 195 KGREVAKELG-IPYYETSV-VAQFGIKDVFDNAIRAAL 230
Cdd:cd04131   139 QGRNLAKQIGaAAYVECSAkTSENSVRDVFEMATLACL 176

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 1907101313  37 IKCVVVGDNAVGKTRLICARACNATLTQYqllathVPTVWaiDQYRvcqevlerSRDVVDDVSVSLRLWDTFG--DHHKD 114
Cdd:cd04133     2 IKCVTVGDGAVGKTCMLISYTSNTFPTDY------VPTVF--DNFS--------ANVVVDGNTVNLGLWDTAGqeDYNRL 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 115 RRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLR-----YADleavnrarRPLARPIKPNE 189
Cdd:cd04133    66 RPLSYRGADVFLLAFSLISKASYENVLKKWIPELRHYAPGVPIVLVGTKLDLRddkqfFAD--------HPGAVPITTAQ 137

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1907101313 190 ilppekGREVAKELGIPYY-ETSVVAQFGIKDVFDNAIRAAL 230
Cdd:cd04133   138 ------GEELRKQIGAAAYiECSSKTQQNVKAVFDAAIKVVL 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 1907101313  35 ETIKC--VVVGDNAVGKTRLICARACNATLTQYqllathVPTVWaiDQYRVCQEVlersrdvvDDVSVSLRLWDTFGDHH 112
Cdd:cd04172     2 QNVKCkiVVVGDSQCGKTALLHVFAKDCFPENY------VPTVF--ENYTASFEI--------DTQRIELSLWDTSGSPY 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 113 KD--RRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRyADLEAVNRARRPLARPIKPNEi 190
Cdd:cd04172    66 YDnvRPLSYPDSDAVLICFDISRPETLDSVLKKWKGEIQEFCPNTKMLLVGCKSDLR-TDVSTLVELSNHRQTPVSYDQ- 143

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1907101313 191 lppekGREVAKELG-IPYYETSVV-AQFGIKDVFDNAIRAAL 230
Cdd:cd04172   144 -----GANMAKQIGaATYIECSALqSENSVRDIFHVATLACV 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 1907101313  31 RPNVETIKCVVVGDNAVGKTRL--ICARACNATltqyqllaTHVPTVWaiDQYRVCQEVlersrdvvDDVSVSLRLWDTF 108
Cdd:cd04174     8 QPLVVRCKLVLVGDVQCGKTAMlqVLAKDCYPE--------TYVPTVF--ENYTACLET--------EEQRVELSLWDTS 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907101313 109 GDHHKD--RRFAYGRSDVVVLCFSIANPNSLHHVKTMWYPEIKHFCPRAPVILVGCQLDLRyADL----EAVNRARRPLA 182
Cdd:cd04174    70 GSPYYDnvRPLCYSDSDAVLLCFDISRPEIFDSALKKWRAEILDYCPSTRILLIGCKTDLR-TDLstlmELSNQKQAPIS 148

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907101313 183 RpikpneilppEKGREVAKELGIP-YYETSV-VAQFGIKDVFDNAiRAALISRRHLQFWKSHLRNVQRPLLQAP 254
Cdd:cd04174   149 Y----------EQGCAMAKQLGAEaYLECSAfTSEKSIHSIFRTA-SLLCINKLSPLAKKSPVRSLSKRLLHLP 211