DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, an important chaperonine family. Hsp40 proteins are characterized by the presence of a J domain, which mediates the interaction with Hsp70. They may contain other domains as well, and the architectures provide a means of classification.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2217328605 146 DSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCVA-PGSEDAFKAVVNA 193
Cdd:cd06257     1 DYYDILGVPPDASDEEIKKAYRKLALKYHPDKNPDdPEAEEKFKEINEA 49

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217328605   14 FYKDTQGVILVYDVGQKDSFDALDAWLAEMKQelgpHGNmENIIFVVCANKIDCTKHRCVDESEGRLWAESKGFLYFETS 93
Cdd:smart00175  69 YYRGAVGALLVYDITNRESFENLENWLKELRE----YAS-PNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETS 143

                           90
                   ....*....|...
gi 2217328605   94 AQTGEGINEMFQT 106
Cdd:smart00175 144 AKTNTNVEEAFEE 156

Rab family protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQelgpHGNmENIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:PLN03108   63 AGQESFRSITRSYYRGAAGALLVYDITRRETFNHLASWLEDARQ----HAN-ANMTIMLIGNKCDLAHRRAVSTEEGEQF 137

                          90       100
                  ....*....|....*....|...
gi 2217328605  82 AESKGFLYFETSAQTGEGINEMF 104
Cdd:PLN03108  138 AKEHGLIFMEASAKTAQNVEEAF 160

DnaJ domain; DnaJ domains (J-domains) are associated with hsp70 heat-shock system and it is thought that this domain mediates the interaction. DnaJ-domain is therefore part of a chaperone (protein folding) system. The T-antigens, although not in Prosite are confirmed as DnaJ containing domains from literature.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2217328605 149 DMLGVKPGASRDEVNKAYRKLAVLLHPDKCV-APGSEDAFKAVVNA 193
Cdd:pfam00226   4 EILGVSPDASDEEIKKAYRKLALKYHPDKNPgDPEAEEKFKEINEA 49

DnaJ molecular chaperone homology domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2217328605  145 KDSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCV--APGSEDAFKAVVNA 193
Cdd:smart00271   1 TDYYEILGVPRDASLDEIKKAYRKLALKYHPDKNPgdKEEAEEKFKEINEA 51

chaperone protein DnaJ; This model represents bacterial forms of DnaJ, part of the DnaK-DnaJ-GrpE chaperone system. The three components typically are encoded by consecutive genes. DnaJ homologs occur in many genomes, typically not near DnaK and GrpE-like genes; most such genes are not included by this family. Eukaryotic (mitochondrial and chloroplast) forms are not included in the scope of this family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2217328605 146 DSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCVAPGSEDAFKAVVNA 193
Cdd:TIGR02349   1 DYYEILGVSKDASEEEIKKAYRKLAKKYHPDRNKDKEAEEKFKEINEA 48

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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQELGPhgnmeNIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:cd00154    57 AGQERFRSITSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYAPP-----NIPIILVGNKSDLEDERQVSTEEAQQF 131

                          90       100
                  ....*....|....*....|....*
gi 2217328605  82 AESKGFLYFETSAQTGEGINEMFQT 106
Cdd:cd00154   132 AKENGLLFFETSAKTGENVDEAFES 156

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217328605   14 FYKDTQGVILVYDVGQKDSFDALDAWLAEMKQelgpHGNmENIIFVVCANKIDCTKHRCVDESEGRLWAESKGFLYFETS 93
Cdd:smart00175  69 YYRGAVGALLVYDITNRESFENLENWLKELRE----YAS-PNVVIMLVGNKSDLEEQRQVSREEAEAFAEEHGLPFFETS 143

                           90
                   ....*....|...
gi 2217328605   94 AQTGEGINEMFQT 106
Cdd:smart00175 144 AKTNTNVEEAFEE 156

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 2217328605  14 FYKDTQGVILVYDVGQKDSFDALDAWLaemkQELGPHGNmENIIFVVCANKIDCTKHRCVDESEGRLWAESKGFLYFETS 93
Cdd:cd01860    70 YYRGAAAAIVVYDITSEESFEKAKSWV----KELQEHGP-PNIVIALAGNKADLESKRQVSTEEAQEYADENGLLFMETS 144

                          90
                  ....*....|..
gi 2217328605  94 AQTGEGINEMFQ 105
Cdd:cd01860   145 AKTGENVNELFT 156

Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic transport and is expressed most highly in polarized epithelial cells. However, trypanosomal Rab, TbRAB18, is upregulated in the BSF (Blood Stream Form) stage and localized predominantly to elements of the Golgi complex. In human and mouse cells, Rab18 has been identified in lipid droplets, organelles that store neutral lipids. 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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQelgpHGNMENIIFVVCANKIDcTKHRCVDESEGRLW 81
Cdd:cd01863    57 AGQERFRTLTSSYYRGAQGVILVYDVTRRDTFDNLDTWLNELDT----YSTNPDAVKMLVGNKID-KENREVTREEGQKF 131

                          90       100
                  ....*....|....*....|...
gi 2217328605  82 AESKGFLYFETSAQTGEGINEMF 104
Cdd:cd01863   132 ARKHNMLFIETSAKTRIGVQQAF 154

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 2217328605  11 RNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQELGPhgnmENIIFVVCANKIDCTKHRCVDESEGRLWAESKGFLYF 90
Cdd:cd00876    64 RDQYIRNGDGFILVYSITSRESFEEIKNIREQILRVKDK----EDVPIVLVGNKCDLENERQVSTEEGEALAEEWGCPFL 139

                          90
                  ....*....|....*..
gi 2217328605  91 ETSAQTGEGINEMFQTF 107
Cdd:cd00876   140 ETSAKTNINIDELFNTL 156

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 2217328605  12 NEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQelgpHGNmENIIFVVCANKIDCTKHRCVDESEGRLWAESKGFLYFE 91
Cdd:cd01868    70 SAYYRGAVGALLVYDITKKSTFENVERWLKELRD----HAD-SNIVIMLVGNKSDLRHLRAVPTEEAKAFAEKNGLSFIE 144

                          90
                  ....*....|....*
gi 2217328605  92 TSAQTGEGINEMFQT 106
Cdd:cd01868   145 TSALDGTNVEEAFKQ 159

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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALdawlAEMKQELGPHGNMENIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:cd04139    56 AGQEDYAAIRDNYFRSGEGFLLVFSITDMESFTAL----AEFREQILRVKEDDNVPLLLVGNKCDLEDKRQVSVEEAANL 131

                          90       100
                  ....*....|....*....|...
gi 2217328605  82 AESKGFLYFETSAQTGEGINEMF 104
Cdd:cd04139   132 AEQWGVNYVETSAKTRANVDKVF 154

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. 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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQELGPHgnmeNIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:cd04111    60 AGQERFRSITRSYYRNSVGVLLVFDITNRESFEHVHDWLEEARSHIQPH----RPVFILVGHKCDLESQRQVTREEAEKL 135

                          90       100
                  ....*....|....*....|...
gi 2217328605  82 AESKGFLYFETSAQTGEGINEMF 104
Cdd:cd04111   136 AKDLGMKYIETSARTGDNVEEAF 158

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 2217328605  16 KDTQGVILVYDVGQKDSFDALDAWLAEMKQELGphgnmENIIFVVCANKIDCTKHRCVDESEGRLWAESKGFLYFETSAQ 95
Cdd:cd01861    71 RDSSVAVVVYDITNRQSFDNTDKWIDDVRDERG-----NDVIIVLVGNKTDLSDKRQVSTEEGEKKAKENNAMFIETSAK 145

                          90
                  ....*....|
gi 2217328605  96 TGEGINEMFQ 105
Cdd:cd01861   146 AGHNVKQLFK 155

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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQelgpHGNMENIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:cd04127    71 AGQERFRSLTTAFFRDAMGFLLMFDLTSEQSFLNVRNWMSQLQA----HAYCENPDIVLIGNKADLPDQREVSERQAREL 146

                          90       100
                  ....*....|....*....|.
gi 2217328605  82 AESKGFLYFETSAQTGEGINE 102
Cdd:cd04127   147 ADKYGIPYFETSAATGQNVEK 167

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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQelgphgNMENIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:cd04110    63 AGQERFRTITSTYYRGTHGVIVVYDVTNGESFVNVKRWLQEIEQ------NCDDVCKVLVGNKNDDPERKVVETEDAYKF 136

                          90       100
                  ....*....|....*....|...
gi 2217328605  82 AESKGFLYFETSAQTGEGINEMF 104
Cdd:cd04110   137 AGQMGISLFETSAKENINVEEMF 159

DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, an important chaperonine family. Hsp40 proteins are characterized by the presence of a J domain, which mediates the interaction with Hsp70. They may contain other domains as well, and the architectures provide a means of classification.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2217328605 146 DSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCVA-PGSEDAFKAVVNA 193
Cdd:cd06257     1 DYYDILGVPPDASDEEIKKAYRKLALKYHPDKNPDdPEAEEKFKEINEA 49

Rab GTPase family 26 (Rab26); Rab26 subfamily. First identified in rat pancreatic acinar cells, Rab26 is believed to play a role in recruiting mature granules to the plasma membrane upon beta-adrenergic stimulation. Rab26 belongs to the Rab functional group III, which are considered key regulators of intracellular vesicle transport during exocytosis. 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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQElgphgNMENIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:cd04112    58 AGQERFRSVTHAYYRDAHALLLLYDVTNKSSFDNIRAWLTEILEY-----AQSDVVIMLLGNKADMSGERVVKREDGERL 132

                          90       100
                  ....*....|....*....|...
gi 2217328605  82 AESKGFLYFETSAQTGEGINEMF 104
Cdd:cd04112   133 AKEYGVPFMETSAKTGLNVELAF 155

DnaJ domain; DnaJ domains (J-domains) are associated with hsp70 heat-shock system and it is thought that this domain mediates the interaction. DnaJ-domain is therefore part of a chaperone (protein folding) system. The T-antigens, although not in Prosite are confirmed as DnaJ containing domains from literature.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2217328605 149 DMLGVKPGASRDEVNKAYRKLAVLLHPDKCV-APGSEDAFKAVVNA 193
Cdd:pfam00226   4 EILGVSPDASDEEIKKAYRKLALKYHPDKNPgDPEAEEKFKEINEA 49

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217328605  13 EFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQElgphgnmENIIFVVCANKIDCTKHR-CVDESEGRLWAESKGFLYFE 91
Cdd:cd00882    71 LLLRGADLILLVVDSTDRESEEDAKLLILRRLRK-------EGIPIILVGNKIDLLEEReVEELLRLEELAKILGVPVFE 143

                          90
                  ....*....|....*
gi 2217328605  92 TSAQTGEGINEMFQT 106
Cdd:cd00882   144 VSAKTGEGVDELFEK 158

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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQELGphgnmENIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:cd04120    57 AGQERFNSITSAYYRSAKGIILVYDITKKETFDDLPKWMKMIDKYAS-----EDAELLLVGNKLDCETDREITRQQGEKF 131

                          90       100
                  ....*....|....*....|....
gi 2217328605  82 A-ESKGFLYFETSAQTGEGINEMF 104
Cdd:cd04120   132 AqQITGMRFCEASAKDNFNVDEIF 155

chaperone protein DnaJ; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2217328605 143 NSKDSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCVAPGSEDAFKAVVNARTAL 197
Cdd:PRK14276    2 NNTEYYDRLGVSKDASQDEIKKAYRKLSKKYHPDINKEPGAEEKYKEVQEAYETL 56

chaperone protein DnaJ; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2217328605 144 SKDSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCVAPGSEDAFKAVVNARTAL 197
Cdd:PRK14298    4 TRDYYEILGLSKDASVEDIKKAYRKLAMKYHPDKNKEPDAEEKFKEISEAYAVL 57

Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap subfamily of the Ras family. It consists of Rap2a, Rap2b, and Rap2c. Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton. In human platelets, Rap2 was shown to interact with the cytoskeleton by binding the actin filaments. In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway. The Rap2 interacting protein 9 (RPIP9) is highly expressed in human breast carcinomas and correlates with a poor prognosis, suggesting a role for Rap2 in breast cancer oncogenesis. Rap2b, but not Rap2a, Rap2c, Rap1a, or Rap1b, is expressed in human red blood cells, where it is believed to be involved in vesiculation. A number of additional effector proteins for Rap2 have been identified, including the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. 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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALdawlAEMKQELGPHGNMENIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:cd04176    57 AGTEQFASMRDLYIKNGQGFIVVYSLVNQQTFQDI----KPMRDQIVRVKGYEKVPIILVGNKVDLESEREVSSAEGRAL 132

                          90       100
                  ....*....|....*....|...
gi 2217328605  82 AESKGFLYFETSAQTGEGINEMF 104
Cdd:cd04176   133 AEEWGCPFMETSAKSKTMVNELF 155

Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small GTPases of the ARF, RAB, RAN, RAS, and SAR subfamilies. Others that could not be classified in this way are predicted to be members of the small GTPase superfamily without predictions of the subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217328605    2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALdawlAEMKQELGPHGNMENIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:smart00010  58 AGQEEFSAMRDQYMRTGEGFLLVYSITDRQSFEEI----AKFREQILRVKDRDDVPIVLVGNKCDLENERVVSTEEGKEL 133

                           90       100
                   ....*....|....*....|....*
gi 2217328605   82 AESKGFLYFETSAQTGEGINEMFQT 106
Cdd:smart00010 134 ARQWGCPFLETSAKERINVDEAFYD 158

chaperone protein DnaJ; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217328605 145 KDSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCVAPGSEDAFKAVVNARTAL 197
Cdd:PRK14299    4 KDYYAILGVPKNASQDEIKKAFKKLARKYHPDVNKSPGAEEKFKEINEAYTVL 56

chaperone protein DnaJ; This model represents bacterial forms of DnaJ, part of the DnaK-DnaJ-GrpE chaperone system. The three components typically are encoded by consecutive genes. DnaJ homologs occur in many genomes, typically not near DnaK and GrpE-like genes; most such genes are not included by this family. Eukaryotic (mitochondrial and chloroplast) forms are not included in the scope of this family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2217328605 146 DSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCVAPGSEDAFKAVVNA 193
Cdd:TIGR02349   1 DYYEILGVSKDASEEEIKKAYRKLAKKYHPDRNKDKEAEEKFKEINEA 48

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 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMK--QELGPHGnmenIIFVVCANKIDCTKHRCVDESEGR 79
Cdd:cd04144    55 AGQEEYTALRDQWIREGEGFILVYSITSRSTFERVERFREQIQrvKDESAAD----VPIMIVGNKCDKVYEREVSTEEGA 130

                          90       100
                  ....*....|....*....|....*..
gi 2217328605  80 LWAESKGFLYFETSAQTGEGINEMFQT 106
Cdd:cd04144   131 ALARRLGCEFIEASAKTNVNVERAFYT 157

molecular chaperone DnaJ;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217328605 145 KDSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKcvAPG---SEDAFKAVVNARTAL 197
Cdd:PRK14279    9 KDFYKELGVSSDASAEEIKKAYRKLARELHPDA--NPGdpaAEERFKAVSEAHDVL 62

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organization, with tandem GTP-binding domains and two EF hand domains (pfam00036) that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDvgqKDSFDALDAWLAEMKQELGphgnmeNIIFVVCANKID 66
Cdd:pfam08477  59 AGQERFRSLHPFYYRGAAAALLVYD---SRTFSNLKYWLRELKKYAG------NSPVILVGNKID 114

rab6; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217328605   2 AGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQELGphgnmENIIFVVCANKIDCTKHRCVDESEGRLW 81
Cdd:PTZ00099   37 AGQERFRSLIPSYIRDSAAAIVVYDITNRQSFENTTKWIQDILNERG-----KDVIIALVGNKTDLGDLRKVTYEEGMQK 111

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2217328605  82 AESKGFLYFETSAQTGEGINEMFQTFYISIVDL 114
Cdd:PTZ00099  112 AQEYNTMFHETSAKAGHNIKVLFKKIAAKLPNL 144

A Ras homolog member I (ARHI); ARHI (A Ras homolog member I) is a member of the Ras family with several unique structural and functional properties. ARHI is expressed in normal human ovarian and breast tissue, but its expression is decreased or eliminated in breast and ovarian cancer. ARHI contains an N-terminal extension of 34 residues (human) that is required to retain its tumor suppressive activity. Unlike most other Ras family members, ARHI is maintained in the constitutively active (GTP-bound) state in resting cells and has modest GTPase activity. ARHI inhibits STAT3 (signal transducers and activators of transcription 3), a latent transcription factor whose abnormal activation plays a critical role in oncogenesis. 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 2217328605  22 ILVYDVGQKDSFDALDAWLAEMKQELGphGNMENIIFVVCANKIDCTKHRCVDESEGRLWAESKGFLYFETSAQTGEGIN 101
Cdd:cd04140    77 ILVYSITSKQSLEELKPIYELICEIKG--NNLEKIPIMLVGNKCDESPSREVSSSEGAALARTWNCAFMETSAKTNHNVQ 154

                  ....
gi 2217328605 102 EMFQ 105
Cdd:cd04140   155 ELFQ 158

DnaJ domain-containing protein [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217328605 143 NSKDSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCVAPGSEdAFKAVVNARTALL 198
Cdd:COG1076     2 QLDDAFELLGLPPDADDAELKRAYRKLQREHHPDRLAAGLPE-EEQRLALQKAAAI 56

chaperone protein DnaJ; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217328605 145 KDSWDMLGVKPGASRDEVNKAYRKLAVLLHPDKCVAPGSEDAFKAVVNARTAL 197
Cdd:PRK14283    5 RDYYEVLGVDRNADKKEIKKAYRKLARKYHPDVSEEEGAEEKFKEISEAYAVL 57