P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHF 80
Cdd:cd04109  66 MLDKYIYGAQAVCLVYDITNSQSFENLEDWLSVVKKVNEESETKPKMVLVGNKTDLEHNRQVTAEKHARFAQENDMESIF 145

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74149432  81 VSAKTGDSVFLCFQKVAAEILGIKLNKAEIEQSQRVVKADIVNYNQ----EPLSRTVNPPRSSMCAVQ 144
Cdd:cd04109 146 VSAKTGDRVFLCFQRIAAELLGVKLSQAELEQSQRVVKADVSRYSErtlrEPVSRSVNKRSNSMCAVM 213

Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown to be a late embryogenesis-abundant (Lea) protein that is regulated by the plant hormone abcisic acid (ABA). In Arabidopsis, Rab28 is expressed during embryo development and is generally restricted to provascular tissues in mature embryos. Unlike maize Rab28, it is not ABA-inducible. Characterization of the human Rab28 homolog revealed two isoforms, which differ by a 95-base pair insertion, producing an alternative sequence for the 30 amino acids at the C-terminus. The two human isoforms are presumably the result of alternative splicing. Since they differ at the C-terminus but not in the GTP-binding region, they are predicted to be targeted to different cellular locations. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHF 80
Cdd:cd04109  66 MLDKYIYGAQAVCLVYDITNSQSFENLEDWLSVVKKVNEESETKPKMVLVGNKTDLEHNRQVTAEKHARFAQENDMESIF 145

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74149432  81 VSAKTGDSVFLCFQKVAAEILGIKLNKAEIEQSQRVVKADIVNYNQ----EPLSRTVNPPRSSMCAVQ 144
Cdd:cd04109 146 VSAKTGDRVFLCFQRIAAELLGVKLSQAELEQSQRVVKADVSRYSErtlrEPVSRSVNKRSNSMCAVM 213

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 74149432     1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESetqPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSshF 80
Cdd:pfam00071  64 LRPLYYRGADGFLLVYDITSRDSFENVKKWVEEILRHADEN---VPIVLVGNKCDLEDQRVVSTEEGEALAKELGLP--F 138

                          90       100
                  ....*....|....*....|...
gi 74149432    81 V--SAKTGDSVFLCFQKVAAEIL 101
Cdd:pfam00071 139 MetSAKTNENVEEAFEELAREIL 161

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   8 GAQGILLVYDITNYQSFENLEDWYSVVKTVSEESetqPLVaLVGNKIDLEHMRTVKADKHLR-FCQENGFSSHF-VSAKT 85
Cdd:COG1100  79 GASLYLFVVDGTREETLQSLYELLESLRRLGKKS---PII-LVLNKIDLYDEEEIEDEERLKeALSEDNIVEVVaTSAKT 154

                        90
                ....*....|....*..
gi 74149432  86 GDSVFLCFQKVAAEILG 102
Cdd:COG1100 155 GEGVEELFAALAEILRG 171

Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown to be a late embryogenesis-abundant (Lea) protein that is regulated by the plant hormone abcisic acid (ABA). In Arabidopsis, Rab28 is expressed during embryo development and is generally restricted to provascular tissues in mature embryos. Unlike maize Rab28, it is not ABA-inducible. Characterization of the human Rab28 homolog revealed two isoforms, which differ by a 95-base pair insertion, producing an alternative sequence for the 30 amino acids at the C-terminus. The two human isoforms are presumably the result of alternative splicing. Since they differ at the C-terminus but not in the GTP-binding region, they are predicted to be targeted to different cellular locations. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHF 80
Cdd:cd04109  66 MLDKYIYGAQAVCLVYDITNSQSFENLEDWLSVVKKVNEESETKPKMVLVGNKTDLEHNRQVTAEKHARFAQENDMESIF 145

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74149432  81 VSAKTGDSVFLCFQKVAAEILGIKLNKAEIEQSQRVVKADIVNYNQ----EPLSRTVNPPRSSMCAVQ 144
Cdd:cd04109 146 VSAKTGDRVFLCFQRIAAELLGVKLSQAELEQSQRVVKADVSRYSErtlrEPVSRSVNKRSNSMCAVM 213

Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432      5 YIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESetqPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSAK 84
Cdd:smart00175  69 YYRGAVGALLVYDITNRESFENLENWLKELREYASPN---VVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETSAK 145

                           90
                   ....*....|....*..
gi 74149432     85 TGDSVFLCFQKVAAEIL 101
Cdd:smart00175 146 TNTNVEEAFEELAREIL 162

Rab GTPase family 11 (Rab11)-like includes Rab11a, Rab11b, and Rab25; Rab11a, Rab11b, and Rab25 are closely related, evolutionary conserved Rab proteins that are differentially expressed. Rab11a is ubiquitously synthesized, Rab11b is enriched in brain and heart and Rab25 is only found in epithelia. Rab11/25 proteins seem to regulate recycling pathways from endosomes to the plasma membrane and to the trans-Golgi network. Furthermore, Rab11a is thought to function in the histamine-induced fusion of tubulovesicles containing H+, K+ ATPase with the plasma membrane in gastric parietal cells and in insulin-stimulated insertion of GLUT4 in the plasma membrane of cardiomyocytes. Overexpression of Rab25 has recently been observed in ovarian cancer and breast cancer, and has been correlated with worsened outcomes in both diseases. In addition, Rab25 overexpression has also been observed in prostate cancer, transitional cell carcinoma of the bladder, and invasive breast tumor cells. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab 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 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWYSVVKtvsEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSAK 84
Cdd:cd01868  72 YYRGAVGALLVYDITKKSTFENVERWLKELR---DHADSNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIETSAL 148

                        90
                ....*....|....*.
gi 74149432  85 TGDSVFLCFQKVAAEI 100
Cdd:cd01868 149 DGTNVEEAFKQLLTEI 164

Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The Rab5-related subfamily includes Rab5 and Rab22 of mammals, Ypt51/Ypt52/Ypt53 of yeast, and RabF of plants. The members of this subfamily are involved in endocytosis and endocytic-sorting pathways. In mammals, Rab5 GTPases localize to early endosomes and regulate fusion of clathrin-coated vesicles to early endosomes and fusion between early endosomes. In yeast, Ypt51p family members similarly regulate membrane trafficking through prevacuolar compartments. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab 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 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWysvVKTVSEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSAK 84
Cdd:cd01860  70 YYRGAAAAIVVYDITSEESFEKAKSW---VKELQEHGPPNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETSAK 146

                        90
                ....*....|....*..
gi 74149432  85 TGDSVFLCFQKVAAEIL 101
Cdd:cd01860 147 TGENVNELFTEIARKLP 163

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432    5 YIYGAQGILLVYDITNYQSFENLEDWYSvvKTVSEESETQPLVA-LVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSA 83
Cdd:PLN03118  82 YYRNAQGIILVYDVTRRETFTNLSDVWG--KEVELYSTNQDCVKmLVGNKVDRESERDVSREEGMALAKEHGCLFLECSA 159

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 74149432   84 KTGDSVFLCFQKVAAEILGIklnKAEIEQSQRVVKADIVnyNQEPLSRTvnPPRSSMCA 142
Cdd:PLN03118 160 KTRENVEQCFEELALKIMEV---PSLLEEGSTAVKRNIL--KQKPEHQP--PPNGGCCS 211

Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab 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 74149432   8 GAQGILLVYDITNYQSFENLEDWYS--VVKTVSEESETQPLVaLVGNKIDLEHMRTVKADKHLRFCQENGFSSHF-VSAK 84
Cdd:cd01862  72 GADCCVLVYDVTNPKSFESLDSWRDefLIQASPRDPENFPFV-VLGNKIDLEEKRQVSTKKAQQWCKSKGNIPYFeTSAK 150

                        90
                ....*....|...
gi 74149432  85 TGDSVFLCFQKVA 97
Cdd:cd01862 151 EAINVDQAFETIA 163

Rab GTPase family 2 (Rab2); Rab2 is localized on cis-Golgi membranes and interacts with Golgi matrix proteins. Rab2 is also implicated in the maturation of vesicular tubular clusters (VTCs), which are microtubule-associated intermediates in transport between the ER and Golgi apparatus. In plants, Rab2 regulates vesicle trafficking between the ER and the Golgi bodies and is important to pollen tube growth. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab 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 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESETqplVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSAK 84
Cdd:cd01866  73 YYRGAAGALLVYDITRRETFNHLTSWLEDARQHSNSNMT---IMLIGNKCDLESRREVSYEEGEAFAREHGLIFMETSAK 149

                        90
                ....*....|....*..
gi 74149432  85 TGDSVFLCFQKVAAEIL 101
Cdd:cd01866 150 TASNVEEAFINTAKEIY 166

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432    5 YIYGAQGILLVYDITNYQSFENLEDWysvVKTVSEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSAK 84
Cdd:PLN03108  75 YYRGAAGALLVYDITRRETFNHLASW---LEDARQHANANMTIMLIGNKCDLAHRRAVSTEEGEQFAKEHGLIFMEASAK 151

                         90
                 ....*....|....*..
gi 74149432   85 TGDSVFLCFQKVAAEIL 101
Cdd:PLN03108 152 TAQNVEEAFIKTAAKIY 168

Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   7 YGAQGILLVYDITNYQSFENLEDWYSVVKT--VSEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSAK 84
Cdd:cd04119  71 KDTQGVLLVYDVTDRQSFEALDSWLKEMKQegGPHGNMENIVVVVCANKIDLTKHRAVSEDEGRLWAESKGFKYFETSAC 150

                ....*
gi 74149432  85 TGDSV 89
Cdd:cd04119 151 TGEGV 155

rab6; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432    1 MLDKYIYGAQGILLVYDITNYQSFENLEDWysvVKTVSEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHF 80
Cdd:PTZ00099  45 LIPSYIRDSAAAIVVYDITNRQSFENTTKW---IQDILNERGKDVIIALVGNKTDLGDLRKVTYEEGMQKAQEYNTMFHE 121

                         90       100
                 ....*....|....*....|
gi 74149432   81 VSAKTGDSVFLCFQKVAAEI 100
Cdd:PTZ00099 122 TSAKAGHNIKVLFKKIAAKL 141

Rab GTPase family 12 (Rab12); Rab12 was first identified in canine cells, where it was localized to the Golgi complex. The specific function of Rab12 remains unknown, and inconsistent results about its cellular localization have been reported. More recent studies have identified Rab12 associated with post-Golgi vesicles, or with other small vesicle-like structures but not with the Golgi complex. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWYSVV-KTVSEESEtqplVALVGNKIDLEHMRTVKADKHLRFCQE-NGFSSHFVS 82
Cdd:cd04120  69 YYRSAKGIILVYDITKKETFDDLPKWMKMIdKYASEDAE----LLLVGNKLDCETDREITRQQGEKFAQQiTGMRFCEAS 144

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 74149432  83 AKTGDSVFLCFQKVAAEIlgikLNKAEIEQSQRVVKADIVNYNQEP-LSRTVNPPRSSM 140
Cdd:cd04120 145 AKDNFNVDEIFLKLVDDI----LKKMPLDILRNELSNSILSLQPEPeIPPELPPPRPHV 199

Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like families; RERG (Ras-related and Estrogen- Regulated Growth inhibitor) and Ras-like 11 are members of a novel subfamily of Ras that were identified based on their behavior in breast and prostate tumors, respectively. RERG expression was decreased or lost in a significant fraction of primary human breast tumors that lack estrogen receptor and are correlated with poor clinical prognosis. Elevated RERG expression correlated with favorable patient outcome in a breast tumor subtype that is positive for estrogen receptor expression. In contrast to most Ras proteins, RERG overexpression inhibited the growth of breast tumor cells in vitro and in vivo. RasL11 was found to be ubiquitously expressed in human tissue, but down-regulated in prostate tumors. Both RERG and RasL11 lack the C-terminal CaaX prenylation motif, where a = an aliphatic amino acid and X = any amino acid, and are localized primarily in the cytoplasm. Both are believed to have tumor suppressor activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   2 LDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESETQPLVaLVGNKIDLEHMRTVKADKHLRFCQENGFSSHFV 81
Cdd:cd04146  66 LERSLRWADGFVLVYSITDRSSFDVVSQLLQLIREIKKRDGEIPVI-LVGNKADLLHSRQVSTEEGQKLALELGCLFFEV 144

                        90       100
                ....*....|....*....|
gi 74149432  82 SAKTG-DSVFLCFQKVAAEI 100
Cdd:cd04146 145 SAAENyLEVQNVFHELCREV 164

Rab GTPase family 14 (Rab14); Rab14 GTPases are localized to biosynthetic compartments, including the rough ER, the Golgi complex, and the trans-Golgi network, and to endosomal compartments, including early endosomal vacuoles and associated vesicles. Rab14 is believed to function in both the biosynthetic and recycling pathways between the Golgi and endosomal compartments. Rab14 has also been identified on GLUT4 vesicles, and has been suggested to help regulate GLUT4 translocation. In addition, Rab14 is believed to play a role in the regulation of phagocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab 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 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESEtqpLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSAK 84
Cdd:cd04122  71 YYRGAAGALMVYDITRRSTYNHLSSWLTDARNLTNPNT---VIFLIGNKADLEAQRDVTYEEAKQFADENGLLFLECSAK 147

                        90
                ....*....|....*.
gi 74149432  85 TGDSVFLCFQKVAAEI 100
Cdd:cd04122 148 TGENVEDAFLETAKKI 163

Rab GTPase family 27a (Rab27a); The Rab27a subfamily consists of Rab27a and its highly homologous isoform, Rab27b. Unlike most Rab proteins whose functions remain poorly defined, Rab27a has many known functions. Rab27a has multiple effector proteins, and depending on which effector it binds, Rab27a has different functions as well as tissue distribution and/or cellular localization. Putative functions have been assigned to Rab27a when associated with the effector proteins Slp1, Slp2, Slp3, Slp4, Slp5, DmSlp, rabphilin, Dm/Ce-rabphilin, Slac2-a, Slac2-b, Slac2-c, Noc2, JFC1, and Munc13-4. Rab27a has been associated with several human diseases, including hemophagocytic syndrome (Griscelli syndrome or GS), Hermansky-Pudlak syndrome, and choroidermia. In the case of GS, a rare, autosomal recessive disease, a Rab27a mutation is directly responsible for the disorder. When Rab27a is localized to the secretory granules of pancreatic beta cells, it is believed to mediate glucose-stimulated insulin secretion, making it a potential target for diabetes therapy. When bound to JFC1 in prostate cells, Rab27a is believed to regulate the exocytosis of prostate- specific markers. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab 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 74149432   9 AQGILLVYDITNYQSFENLEDWYSVVKTvSEESEtQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSAKTGDS 88
Cdd:cd04127  87 AMGFLLMFDLTSEQSFLNVRNWMSQLQA-HAYCE-NPDIVLIGNKADLPDQREVSERQARELADKYGIPYFETSAATGQN 164

                .
gi 74149432  89 V 89
Cdd:cd04127 165 V 165

Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. p21Ras couples receptor Tyr kinases and G protein receptors to protein kinase cascades

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432      1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVsEESETQPLVaLVGNKIDLEHMRTVKADKHLRFCQENGFSSHF 80
Cdd:smart00173  64 MRDQYMRTGEGFLLVYSITDRQSFEEIKKFREQILRV-KDRDDVPIV-LVGNKCDLESERVVSTEEGKELARQWGCPFLE 141

                           90       100
                   ....*....|....*....|
gi 74149432     81 VSAKTGDSVFLCFQKVAAEI 100
Cdd:smart00173 142 TSAKERVNVDEAFYDLVREI 161

Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily consists of the highly homologous RalA and RalB. Ral proteins are believed to play a crucial role in tumorigenesis, metastasis, endocytosis, and actin cytoskeleton dynamics. Despite their high sequence similarity (>80% sequence identity), nonoverlapping and opposing functions have been assigned to RalA and RalBs in tumor migration. In human bladder and prostate cancer cells, RalB promotes migration while RalA inhibits it. A Ral-specific set of GEFs has been identified that are activated by Ras binding. This RalGEF activity is enhanced by Ras binding to another of its target proteins, phosphatidylinositol 3-kinase (PI3K). Ral effectors include RLIP76/RalBP1, a Rac/cdc42 GAP, and the exocyst (Sec6/8) complex, a heterooctomeric protein complex that is involved in tethering vesicles to specific sites on the plasma membrane prior to exocytosis. In rat kidney cells, RalB is required for functional assembly of the exocyst and for localizing the exocyst to the leading edge of migrating cells. In human cancer cells, RalA is required to support anchorage-independent proliferation and RalB is required to suppress apoptosis. RalA has been shown to localize to the plasma membrane while RalB is localized to the intracellular vesicles. Most Ras 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 Ras 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 74149432   3 DKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVsEESETQPLVaLVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVS 82
Cdd:cd04139  66 DNYFRSGEGFLLVFSITDMESFTALAEFREQILRV-KEDDNVPLL-LVGNKCDLEDKRQVSVEEAANLAEQWGVNYVETS 143

                        90
                ....*....|....*...
gi 74149432  83 AKTGDSVFLCFQKVAAEI 100
Cdd:cd04139 144 AKTRANVDKVFFDLVREI 161

GTPase SAR1 family domain [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   8 GAQGILLVYDITNYQSFENLEDWYSVVKTVSEESetqPLVaLVGNKIDLEHMRTVKADKHLR-FCQENGFSSHF-VSAKT 85
Cdd:COG1100  79 GASLYLFVVDGTREETLQSLYELLESLRRLGKKS---PII-LVLNKIDLYDEEEIEDEERLKeALSEDNIVEVVaTSAKT 154

                        90
                ....*....|....*..
gi 74149432  86 GDSVFLCFQKVAAEILG 102
Cdd:COG1100 155 GEGVEELFAALAEILRG 171

Rab GTPase-like family 4 (Rab-like4); RabL4 (Rab-like4) subfamily. RabL4s are novel proteins that have high sequence similarity with Rab family members, but display features that are distinct from Rabs, and have been termed Rab-like. As in other Rab-like proteins, RabL4 lacks a prenylation site at the C-terminus. The specific function of RabL4 remains unknown.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESETQPLvaLVGNKIDLEHMRTVKADKHLRFCQENGFSSHF 80
Cdd:cd04101  69 MVENVWEQPAVVCVVYDVTNEVSFNNCSRWINRVRTHSHGLHTPGV--LVGNKCDLTDRREVDAAQAQALAQANTLKFYE 146

                        90
                ....*....|....*...
gi 74149432  81 VSAKTGDSVFLCFQKVAA 98
Cdd:cd04101 147 TSAKEGVGYEAPFLSLAR 164

Rab GTPase families 18 (Rab18) and 32 (Rab32); Rab38/Rab32 subfamily. Rab32 and Rab38 are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP). Rab38 has been shown to be melanocyte-specific. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   1 MLDKYIYGAQGILLVYDITNYQSFENLEDWY----SVVKTVSEESetQPLVaLVGNKIDLEHMRT-VKADKHLRFCQENG 75
Cdd:cd04107  66 MTRVYYKGAVGAIIVFDVTRPSTFEAVLKWKadldSKVTLPNGEP--IPAL-LLANKCDLKKERLaKDPEQMDQFCKENG 142

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 74149432  76 FSSHFV-SAKTGDSVFLCFQKVAAEILgikLNKAEIEQSQRVVKADIVNYNQEPLS 130
Cdd:cd04107 143 FIGWFEtSAKENINIEEAMRFLVKNIL---KNDKGLQSPEPDEDNVIDLKQETTTS 195

Rab GTPase family 19 (Rab19); Rab19 subfamily. Rab19 proteins are associated with Golgi stacks. Similarity analysis indicated that Rab41 is closely related to Rab19. However, the function of these Rabs is not yet characterized. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab 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 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWysvVKTVSEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENG-FSSHFVSA 83
Cdd:cd01864  72 YYRSANGAIIAYDITRRSSFESVPHW---IEEVEKYGASNVVLLLIGNKCDLEEQREVLFEEACTLAEHYGiLAVLETSA 148

                        90
                ....*....|....*..
gi 74149432  84 KTGDSVFLCFQKVAAEI 100
Cdd:cd01864 149 KESSNVEEAFLLMATEL 165

Rab GTPase family 30 (Rab30); Rab30 subfamily. Rab30 appears to be associated with the Golgi stack. It is expressed in a wide variety of tissue types and in humans maps to chromosome 11. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab 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 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWysvVKTVSEESETQPLVALVGNKIDLEHMRTVKADKHLRFCQENGFSSHFVSAK 84
Cdd:cd04114  76 YYRSANALILTYDITCEESFRCLPEW---LREIEQYANNKVITILVGNKIDLAERREVSQQRAEEFSDAQDMYYLETSAK 152

                        90
                ....*....|....*..
gi 74149432  85 TGDSVFLCFQKVAAEIL 101
Cdd:cd04114 153 ESDNVEKLFLDLACRLI 169

Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active (GTP-bound) Ras interacts with several effector proteins that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF and NORE/MST1. Most Ras 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 Ras 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 74149432   1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVsEESETQPLVaLVGNKIDLEHmRTVKADKHLRFCQENGFSSHF 80
Cdd:cd04138  65 MRDQYMRTGEGFLCVFAINSRKSFEDIHTYREQIKRV-KDSDDVPMV-LVGNKCDLAA-RTVSTRQGQDLAKSYGIPYIE 141

                        90       100
                ....*....|....*....|
gi 74149432  81 VSAKTGDSVFLCFQKVAAEI 100
Cdd:cd04138 142 TSAKTRQGVEEAFYTLVREI 161

Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats. In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with N|PM-ALK, it may provide a target for cancer treatments. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWY-------SVVKTVseesetqplvaLVGNKIDLEHMRTVKADKHLRFCQENGFS 77
Cdd:cd04110  75 YYRGTHGVIVVYDVTNGESFVNVKRWLqeieqncDDVCKV-----------LVGNKNDDPERKVVETEDAYKFAGQMGIS 143

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 74149432  78 SHFVSAKTGDSVFLCFQKVAAEILGIKLN---KAEIEQSQRVVKA 119
Cdd:cd04110 144 LFETSAKENINVEEMFNCITELVLRAKKDnlaKQQQQQQNDVVKL 188

Rab GTPase family 33 includes Rab33A and Rab33B; Rab33B/Rab33A subfamily. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways. Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab 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 74149432   1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYsvvktvsEESETQPLVA-----LVGNKIDLEHMRTVKADKHLRFCQENG 75
Cdd:cd04115  68 MVQHYYRNVHAVVFVYDVTNMASFHSLPSWI-------EECEQHSLPNevpriLVGNKCDLREQIQVPTDLAQRFADAHS 140

                        90       100
                ....*....|....*....|...
gi 74149432  76 FSSHFVSAKTG------DSVFLC 92
Cdd:cd04115 141 MPLFETSAKDPsendhvEAIFMT 163

Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap subfamily of the Ras family. It can be further divided into the Rap1a and Rap1b isoforms. In humans, Rap1a and Rap1b share 95% sequence homology, but are products of two different genes located on chromosomes 1 and 12, respectively. Rap1a is sometimes called smg p21 or Krev1 in the older literature. Rap1 proteins are believed to perform different cellular functions, depending on the isoform, its subcellular localization, and the effector proteins it binds. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and the microsomal membrane of pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. High expression of Rap1 has been observed in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines; interestingly, in the SCCs, the active GTP-bound form localized to the nucleus, while the inactive GDP-bound form localized to the cytoplasm. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap1a, which is stimulated by T-cell receptor (TCR) activation, is a positive regulator of T cells by directing integrin activation and augmenting lymphocyte responses. In murine hippocampal neurons, Rap1b determines which neurite will become the axon and directs the recruitment of Cdc42, which is required for formation of dendrites and axons. In murine platelets, Rap1b is required for normal homeostasis in vivo and is involved in integrin activation. Most Ras 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 Ras 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 74149432   1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKTVsEESETQPLVaLVGNKIDLEHMRTVKADKHLRFCQENGFSSHF 80
Cdd:cd04175  65 MRDLYMKNGQGFVLVYSITAQSTFNDLQDLREQILRV-KDTEDVPMI-LVGNKCDLEDERVVGKEQGQNLARQWGCAFLE 142

                ....*
gi 74149432  81 VSAKT 85
Cdd:cd04175 143 TSAKA 147

Rab GTPase-like family 2 (Rab-like2); RabL2 (Rab-like2) subfamily. RabL2s are novel Rab proteins identified recently which display features that are distinct from other Rabs, and have been termed Rab-like. RabL2 contains RabL2a and RabL2b, two very similar Rab proteins that share > 98% sequence identity in humans. RabL2b maps to the subtelomeric region of chromosome 22q13.3 and RabL2a maps to 2q13, a region that suggests it is also a subtelomeric gene. Both genes are believed to be expressed ubiquitously, suggesting that RabL2s are the first example of duplicated genes in human proximal subtelomeric regions that are both expressed actively. Like other Rab-like proteins, RabL2s lack a prenylation site at the C-terminus. The specific functions of RabL2a and RabL2b remain unknown. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   1 MLDKYIYGAQGILLVYDITNYQSFENLEDWYSVVKtvsEESETQPLVaLVGNKIDLEHMRTVKAdkhLRFCQENGFSSHF 80
Cdd:cd04124  65 MHASYYHKAHACILVFDVTRKITYKNLSKWYEELR---EYRPEIPCI-VVANKIDLDPSVTQKK---FNFAEKHNLPLYY 137

                        90
                ....*....|....
gi 74149432  81 VSAKTGDSVFLCFQ 94
Cdd:cd04124 138 VSAADGTNVVKLFQ 151

Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists primarily in the GTP-bound state, having a low intrinsic GTPase activity; it is not efficiently geranyl-geranylated at the C-terminus; it does not form a detectable complex with Rab GDP-dissociation inhibitors (GDIs); and it has recently been shown to undergo tyrosine phosphorylation when overexpressed in vitro. The specific function of Rab24 still remains unknown. It is found in a transport route between ER-cis-Golgi and late endocytic compartments. It is putatively involved in an autophagic pathway, possibly directing misfolded proteins in the ER to degradative pathways. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWYSVVKTVSEESEtqplVALVGNKIDLehmrtVKADKHLR---------FCQENG 75
Cdd:cd04118  70 YYRGAKAAIVCYDLTDSSSFERAKFWVKELQNLEEHCK----IYLCGTKSDL-----IEQDRSLRqvdfhdvqdFADEIK 140

                        90       100       110
                ....*....|....*....|....*....|..
gi 74149432  76 fSSHF-VSAKTGDSVFLCFQKVAAEILGIKLN 106
Cdd:cd04118 141 -AQHFeTSSKTGQNVDELFQKVAEDFVSRANN 171

Rab GTPase family 20 (Rab20); Rab20 is one of several Rab proteins that appear to be restricted in expression to the apical domain of murine polarized epithelial cells. It is expressed on the apical side of polarized kidney tubule and intestinal epithelial cells, and in non-polarized cells. It also localizes to vesico-tubular structures below the apical brush border of renal proximal tubule cells and in the apical region of duodenal epithelial cells. Rab20 has also been shown to colocalize with vacuolar H+-ATPases (V-ATPases) in mouse kidney cells, suggesting a role in the regulation of V-ATPase traffic in specific portions of the nephron. It was also shown to be one of several proteins whose expression is upregulated in human myelodysplastic syndrome (MDS) patients. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 74149432   5 YIYGAQGILLVYDITNYQSFENLEDWY-SVVKTVSEESetqpLVALVGNKIDL 56
Cdd:cd04126  64 YCRGAAAVILTYDVSNVQSLEELEDRFlGLTDTANEDC----LFAVVGNKLDL 112