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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1054397473    1 MKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEE 80
Cdd:smart00175  39 TKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVYDITNRESFENLENWLKELREYASPNVVIMLVGNKSDLE 118

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1054397473   81 QKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLTELVLQ 125
Cdd:smart00175 119 EQRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEAFEELAREILK 163

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEEQ 81
Cdd:PLN03108   46 RMITIDNKPIKLQIWDTAGQESFRSITRSYYRGAAGALLVYDITRRETFNHLASWLEDARQHANANMTIMLIGNKCDLAH 125

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1054397473  82 KRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLTELVLQ 125
Cdd:PLN03108  126 RRAVSTEEGEQFAKEHGLIFMEASAKTAQNVEEAFIKTAAKIYK 169

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 1054397473   4 IEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISS-ERSYQHI-MKWVSDVDEYAPEGVQKILIGNKADEEQ 81
Cdd:TIGR00231  44 IEEDGKTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVFDIVIlVLDVEEIlEKQTKEIIHHADSGVPIILVGNKIDLKD 123

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1054397473  82 kRQVGREQGQQLAKEYGMDFYETSACTNLNIKESF 116
Cdd:TIGR00231 124 -ADLKTHVASEFAKLNGEPIIPLSAETGKNIDSAF 157

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1054397473    1 MKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEE 80
Cdd:smart00175  39 TKTIEVDGKRVKLQIWDTAGQERFRSITSSYYRGAVGALLVYDITNRESFENLENWLKELREYASPNVVIMLVGNKSDLE 118

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1054397473   81 QKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLTELVLQ 125
Cdd:smart00175 119 EQRQVSREEAEAFAEEHGLPFFETSAKTNTNVEEAFEELAREILK 163

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. 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 mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. 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. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1054397473   1 MKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEE 80
Cdd:cd00154    39 SKTIEVDGKKVKLQIWDTAGQERFRSITSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYAPPNIPIILVGNKSDLE 118

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1054397473  81 QKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLTE 121
Cdd:cd00154   119 DERQVSTEEAQQFAKENGLLFFETSAKTGENVDEAFESLAR 159

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. 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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEEQ 81
Cdd:cd01869    42 RTIELDGKTVKLQIWDTAGQERFRTITSSYYRGAHGIIIVYDVTDQESFNNVKQWLQEIDRYASENVNKLLVGNKCDLTD 121

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1054397473  82 KRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLT 120
Cdd:cd01869   122 KKVVDYTEAKEFADELGIPFLETSAKNATNVEEAFMTMA 160

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 1054397473   1 MKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEE 80
Cdd:cd04120    39 IKTVELRGKKIRLQIWDTAGQERFNSITSAYYRSAKGIILVYDITKKETFDDLPKWMKMIDKYASEDAELLLVGNKLDCE 118

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1054397473  81 QKRQVGREQGQQLAKEY-GMDFYETSACTNLNIKESFTRLTELVLQahRKELEGLRMRASN 140
Cdd:cd04120   119 TDREITRQQGEKFAQQItGMRFCEASAKDNFNVDEIFLKLVDDILK--KMPLDILRNELSN 177

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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEEQ 81
Cdd:cd01860    41 QTVNLDDTTVKFEIWDTAGQERYRSLAPMYYRGAAAAIVVYDITSEESFEKAKSWVKELQEHGPPNIVIALAGNKADLES 120

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1054397473  82 KRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLTELVL 124
Cdd:cd01860   121 KRQVSTEEAQEYADENGLLFMETSAKTGENVNELFTEIARKLP 163

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 1054397473   1 MKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEE 80
Cdd:cd01864    42 MKTLEIQGKRVKLQIWDTAGQERFRTITQSYYRSANGAIIAYDITRRSSFESVPHWIEEVEKYGASNVVLLLIGNKCDLE 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1054397473  81 QKRQVGREQGQQLAKEYGMDF-YETSACTNLNIKESFTRL-TEL 122
Cdd:cd01864   122 EQREVLFEEACTLAEHYGILAvLETSAKESSNVEEAFLLMaTEL 165

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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEEQ 81
Cdd:cd01866    44 RMITIDGKQIKLQIWDTAGQESFRSITRSYYRGAAGALLVYDITRRETFNHLTSWLEDARQHSNSNMTIMLIGNKCDLES 123

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1054397473  82 KRQVGREQGQQLAKEYGMDFYETSACTNLNIKESF 116
Cdd:cd01866   124 RREVSYEEGEAFAREHGLIFMETSAKTASNVEEAF 158

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. 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 1054397473   1 MKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEE 80
Cdd:cd01865    40 VKTVYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILMYDITNEESFNAVQDWSTQIKTYSWDNAQVILVGNKCDME 119

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1054397473  81 QKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLTELV 123
Cdd:cd01865   120 DERVVSAERGRQLADQLGFEFFEASAKENINVKQVFERLVDII 162

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These 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: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs 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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEY-APEGVQKILIGNKADEE 80
Cdd:cd00876    38 KQIVVDGETYTLDILDTAGQEEFSAMRDQYIRNGDGFILVYSITSRESFEEIKNIREQILRVkDKEDVPIVLVGNKCDLE 117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1054397473  81 QKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLT 120
Cdd:cd00876   118 NERQVSTEEGEALAEEWGCPFLETSAKTNINIDELFNTLV 157

Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways through the Golgi and from endosomes to the Golgi. Rab6A of mammals is implicated in retrograde transport through the Golgi stack, and is also required for a slow, COPI-independent, retrograde transport pathway from the Golgi to the endoplasmic reticulum (ER). This pathway may allow Golgi residents to be recycled through the ER for scrutiny by ER quality-control systems. Yeast Ypt6p, the homolog of the mammalian Rab6 GTPase, is not essential for cell viability. Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER trafficking. 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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEEQ 81
Cdd:cd01861    40 KTMYVDDKTVRLQLWDTAGQERFRSLIPSYIRDSSVAVVVYDITNRQSFDNTDKWIDDVRDERGNDVIIVLVGNKTDLSD 119

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1054397473  82 KRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLTE 121
Cdd:cd01861   120 KRQVSTEEGEKKAKENNAMFIETSAKAGHNVKQLFKKIAQ 159

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 1054397473   1 MKTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEE 80
Cdd:cd04114    46 IKTVEIKGEKIKLQIWDTAGQERFRSITQSYYRSANALILTYDITCEESFRCLPEWLREIEQYANNKVITILVGNKIDLA 125

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1054397473  81 QKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRL-TELV 123
Cdd:cd04114   126 ERREVSQQRAEEFSDAQDMYYLETSAKESDNVEKLFLDLaCRLI 169

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 1054397473   8 GIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYA-PEGVQKILIGNKADEEQKRQVG 86
Cdd:cd04127    60 AFRVHLQLWDTAGQERFRSLTTAFFRDAMGFLLMFDLTSEQSFLNVRNWMSQLQAHAyCENPDIVLIGNKADLPDQREVS 139

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1054397473  87 REQGQQLAKEYGMDFYETSACTNLNIKESFTRLTELVLQ 125
Cdd:cd04127   140 ERQARELADKYGIPYFETSAATGQNVEKAVETLLDLIMK 178

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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYAPEGVQKILIGNKADEEQ 81
Cdd:cd04122    42 RIIEVNGQKIKLQIWDTAGQERFRAVTRSYYRGAAGALMVYDITRRSTYNHLSSWLTDARNLTNPNTVIFLIGNKADLEA 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1054397473  82 KRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLTELVLQ 125
Cdd:cd04122   122 QRDVTYEEAKQFADENGLLFLECSAKTGENVEDAFLETAKKIYQ 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 1054397473    2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKW------VSDVDEyapegVQKILIGN 75
Cdd:smart00173  39 KQIEIDGEVCLLDILDTAGQEEFSAMRDQYMRTGEGFLLVYSITDRQSFEEIKKFreqilrVKDRDD-----VPIVLVGN 113

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1054397473   76 KADEEQKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFtrlTELVLQAHRK 129
Cdd:smart00173 114 KCDLESERVVSTEEGKELARQWGCPFLETSAKERVNVDEAF---YDLVREIRKK 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 1054397473   2 KTIEVD-GIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDE---YAPEG-VQKILIGNK 76
Cdd:cd04107    40 KVIEWDpNTVVRLQLWDIAGQERFGGMTRVYYKGAVGAIIVFDVTRPSTFEAVLKWKADLDSkvtLPNGEpIPALLLANK 119

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1054397473  77 ADEEQKR-QVGREQGQQLAKEYGM-DFYETSACTNLNIKESFTRLTELVL 124
Cdd:cd04107   120 CDLKKERlAKDPEQMDQFCKENGFiGWFETSAKENINIEEAMRFLVKNIL 169

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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERY-QTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEYA-PEGVQKILIGNKADE 79
Cdd:cd04115    42 RTVEIDGERIKVQLWDTAGQERFrKSMVQHYYRNVHAVVFVYDVTNMASFHSLPSWIEECEQHSlPNEVPRILVGNKCDL 121

                          90       100
                  ....*....|....*....|....*..
gi 1054397473  80 EQKRQVGREQGQQLAKEYGMDFYETSA 106
Cdd:cd04115   122 REQIQVPTDLAQRFADAHSMPLFETSA 148

Rat sarcoma (Ras) family 2 of small guanosine triphosphatases (GTPases); The Ras2 subfamily, found exclusively in fungi, was first identified in Ustilago maydis. In U. maydis, Ras2 is regulated by Sql2, a protein that is homologous to GEFs (guanine nucleotide exchange factors) of the CDC25 family. Ras2 has been shown to induce filamentous growth, but the signaling cascade through which Ras2 and Sql2 regulate cell morphology is not known. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKW---VSDVDEYAPEGVQKILIGNKAD 78
Cdd:cd04144    38 KQVVVDGQPCMLEVLDTAGQEEYTALRDQWIREGEGFILVYSITSRSTFERVERFreqIQRVKDESAADVPIMIVGNKCD 117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1054397473  79 EEQKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRLTELVLQA 126
Cdd:cd04144   118 KVYEREVSTEEGAALARRLGCEFIEASAKTNVNVERAFYTLVRALRQQ 165

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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKWVSDVDEY-APEGVQKILIGNKADEE 80
Cdd:cd04139    39 KKVVLDGEEVQLNILDTAGQEDYAAIRDNYFRSGEGFLLVFSITDMESFTALAEFREQILRVkEDDNVPLLLVGNKCDLE 118

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1054397473  81 QKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRL 119
Cdd:cd04139   119 DKRQVSVEEAANLAEQWGVNYVETSAKTRANVDKVFFDL 157

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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIM------KWVSDVDEyapegVQKILIGN 75
Cdd:cd04138    40 KQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINSRKSFEDIHtyreqiKRVKDSDD-----VPMVLVGN 114

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1054397473  76 KADEEqKRQVGREQGQQLAKEYGMDFYETSACTNLNIKESFTRL 119
Cdd:cd04138   115 KCDLA-ARTVSTRQGQDLAKSYGIPYIETSAKTRQGVEEAFYTL 157

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 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQgIFLV-YDISSERSYQHI-MKWVSDVDEYAPeGVQKILIGNKAD- 78
Cdd:cd00157    39 ANVTVDGKQVNLGLWDTAGQEEYDRLRPLSYPQTD-VFLLcFSVDSPSSFENVkTKWYPEIKHYCP-NVPIILVGTKIDl 116

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1054397473  79 ----------EEQKRQVGREQGQQLAKEYGMDFY-ETSACTNLNIKESF 116
Cdd:cd00157   117 rddgntlkklEKKQKPITPEEGEKLAKEIGAVKYmECSALTQEGLKEVF 165

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 1054397473    3 TIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIM-KWVSDVDEYAPeGVQKILIGNKAD--- 78
Cdd:smart00174  38 DVEVDGKPVELGLWDTAGQEDYDRLRPLSYPDTDVFLICFSVDSPASFENVKeKWYPEVKHFCP-NVPIILVGTKLDlrn 116

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1054397473   79 -----EEQKRQ----VGREQGQQLAKEYG-MDFYETSACTNLNIKESFTRLTELVLQA 126
Cdd:smart00174 117 dkstlEELSKKkqepVTYEQGQALAKRIGaVKYLECSALTQEGVREVFEEAIRAALNK 174

Ras-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1054397473   2 KTIEVDGIKVRIQIWDTAGQERYQTITKQYYRRAQGIFLVYDISSERSYQHIMKW------VSDVDEyapegVQKILIGN 75
Cdd:PTZ00369   44 KQCVIDEETCLLDILDTAGQEEYSAMRDQYMRTGQGFLCVYSITSRSSFEEIASFreqilrVKDKDR-----VPMILVGN 118