| IED ID | IndEnz0005000079 |
| Enzyme Type ID | lipase000079 |
| Protein Name |
Ras-related protein Rab-7a EC 3.6.5.2 |
| Gene Name | RAB7A RAB7 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MTSRKKVLLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVFDVTAPNTFKTLDSWRDEFLIQASPRDPENFPFVVLGNKIDLENRQVATKRAQAWCYSKNNIPYFETSAKEAINVEQAFQTIARNALKQETEVELYNEFPEPIKLDKNDRAKASAESCSC |
| Enzyme Length | 207 |
| Uniprot Accession Number | P51149 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2; Evidence={ECO:0000269|PubMed:20028791};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000269|PubMed:20028791}; |
| DNA Binding | |
| EC Number | 3.6.5.2 |
| Enzyme Function | FUNCTION: Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins playing a key role in the regulation of endo-lysosomal trafficking. Governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transportor mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. Also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays a role in the fusion of phagosomes with lysosomes. Plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Microbial pathogens possess survival strategies governed by RAB7A, sometimes by employing RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A function (e.g. Mycobacterium). In concert with RAC1, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. Controls the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA (PubMed:11179213, PubMed:12944476, PubMed:14617358, PubMed:20028791, PubMed:21255211). Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation. Involved in the ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway (By similarity). Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). Required for vesicular trafficking and cell surface expression of ACE2 (PubMed:33147445). May play a role in PRPH neuronal intermediate filament assembly (By similarity). {ECO:0000250|UniProtKB:P51150, ECO:0000269|PubMed:11179213, ECO:0000269|PubMed:12944476, ECO:0000269|PubMed:14617358, ECO:0000269|PubMed:20028791, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:33147445}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 15..22; /note="GTP"; /evidence="ECO:0000269|PubMed:15933719, ECO:0000269|PubMed:20028791"; NP_BIND 34..40; /note="GTP"; /evidence="ECO:0000269|PubMed:15933719, ECO:0000269|PubMed:20028791"; NP_BIND 63..67; /note="GTP"; /evidence="ECO:0000269|PubMed:15933719, ECO:0000269|PubMed:20028791"; NP_BIND 125..128; /note="GTP"; /evidence="ECO:0000269|PubMed:15933719, ECO:0000269|PubMed:20028791"; NP_BIND 156..157; /note="GTP"; /evidence="ECO:0000269|PubMed:15933719, ECO:0000269|PubMed:20028791" |
| Features | Beta strand (7); Chain (1); Erroneous gene model prediction (1); Erroneous translation (2); Helix (8); Initiator methionine (1); Lipidation (2); Modified residue (3); Motif (1); Mutagenesis (7); Natural variant (5); Nucleotide binding (5); Sequence conflict (4); Turn (1) |
| Keywords | 3D-structure;Acetylation;Autophagy;Charcot-Marie-Tooth disease;Cytoplasmic vesicle;Disease variant;Endosome;GTP-binding;Host-virus interaction;Hydrolase;Lipid degradation;Lipid droplet;Lipid metabolism;Lipoprotein;Lysosome;Membrane;Methylation;Mitochondrion;Neurodegeneration;Neuropathy;Nucleotide-binding;Phosphoprotein;Prenylation;Protein transport;Reference proteome;Transport |
| Interact With | Q8WXF7; Q32Q52; Q9UNS2; Q02535; Q9BXW6; Q96NA2; Q9UNE7; Q96JC1; Q9GZS3 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasmic vesicle, phagosome membrane {ECO:0000269|PubMed:12944476, ECO:0000269|PubMed:21255211}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Late endosome membrane {ECO:0000269|PubMed:12944476, ECO:0000269|PubMed:14617358, ECO:0000269|PubMed:16176980, ECO:0000269|PubMed:20028791, ECO:0000269|PubMed:28325809}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Lysosome membrane {ECO:0000269|PubMed:12944476, ECO:0000269|PubMed:20028791}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Melanosome membrane {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:20028791}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Lipid droplet {ECO:0000250|UniProtKB:P51150}. Endosome membrane {ECO:0000269|PubMed:22431521}; Peripheral membrane protein {ECO:0000305}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:P51150}. Mitochondrion membrane {ECO:0000305|PubMed:34432599}; Peripheral membrane protein {ECO:0000305}. Note=Colocalizes with OSBPL1A at the late endosome (PubMed:16176980). Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. Recruited to phagosomes containing S.aureus or Mycobacterium (PubMed:21255211). Lipid droplet localization is increased upon ADRB2 stimulation (By similarity). Recruited to damaged mitochondria during mitophagy in a RIMOC1-dependent manner (PubMed:34432599). {ECO:0000250|UniProtKB:P51150, ECO:0000269|PubMed:16176980, ECO:0000269|PubMed:21255211, ECO:0000269|PubMed:34432599}. |
| Modified Residue | MOD_RES 2; /note="N-acetylthreonine"; /evidence="ECO:0007744|PubMed:25944712"; MOD_RES 72; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 207; /note="Cysteine methyl ester"; /evidence="ECO:0000250" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (5) |
| Cross Reference PDB | 1T91; 1YHN; 3LAW; 6IYB; 6WCW; |
| Mapped Pubmed ID | 10036229; 10490598; 10508610; 10618392; 10699464; 10724160; 10873802; 10958683; 10967094; 11141079; 11145705; 11185749; 11389151; 11675392; 11696321; 11756552; 11773441; 11784792; 11803464; 11804587; 11948177; 12034881; 12054610; 12198549; 12242347; 12364329; 12376551; 12456725; 12464619; 12480817; 12773384; 12850305; 12860998; 12907671; 14514689; 14644159; 15099588; 15138286; 15169870; 15186776; 15260990; 15280044; 15340014; 15681833; 15814684; 15996637; 16002401; 16055087; 16282324; 16339170; 1648736; 16507994; 1660188; 16630611; 16631113; 16636067; 16702231; 16762923; 16962593; 16965270; 17027967; 17028588; 17064668; 17114793; 17244649; 17269730; 17283181; 17353931; 17411337; 17540176; 17583407; 17625594; 17916560; 18006505; 18039930; 18046453; 18218625; 18272684; 18347018; 18501189; 18532927; 18787122; 18955491; 18974300; 19367725; 19372461; 19463016; 19534724; 19564404; 19603039; 19651702; 19738201; 19805454; 19956673; 20098737; 20116244; 20184954; 20233848; 20305638; 20363736; 20434987; 20460433; 20472552; 20562859; 20679435; 20709679; 20711168; 20711500; 20797862; 20847427; 20851766; 20974968; 21119010; 2115402; 21169990; 21378159; 21438969; 21669283; 21683469; 21730051; 21911578; 22072966; 22115783; 22304920; 22496312; 22593156; 22608513; 22638108; 22665057; 22673115; 22734669; 22970203; 22971344; 23084991; 23188822; 23220125; 23351085; 23416715; 23536683; 23562278; 23645161; 23650620; 23707487; 23733193; 24023390; 24355937; 24498653; 24505328; 24521780; 24584464; 24659802; 25080504; 25341920; 25367362; 25565581; 25566515; 25668492; 25770103; 25896765; 25963737; 26038114; 26299518; 26348397; 26399387; 26496610; 26541268; 26598554; 26638075; 27070490; 27246931; 27278019; 27378698; 27383256; 27588602; 27791088; 27888097; 28222213; 28336235; 28415797; 28486133; 28600323; 28656962; 28716909; 28825699; 28860274; 28860633; 29099291; 29158324; 29358323; 29360040; 29364868; 29437530; 29505800; 29510700; 29514857; 29769411; 30012887; 30061681; 30100068; 30616015; 30627666; 30721249; 30765602; 30808710; 30816458; 30918899; 30926795; 31079930; 31085713; 31389670; 31544984; 31578588; 31600783; 31619485; 31636202; 31662325; 31664461; 31871319; 32280996; 32302585; 32326241; 32521275; 32591494; 32632011; 32949647; 33144569; 33846303; 34383013; 7559638; 7957092; 7991565; 8107774; 8164745; 8349690; 8375503; 8513495; 8522602; 8543060; 8631982; 8642258; 8645157; 8662891; 8662963; 8670801; 8756646; 8798539; 8805223; 8816443; 8836150; 8909537; 9013646; 9020161; 9405671; 9705280; 9792683; 9822598; 9829970; 9843499; 9988689; |
| Motif | MOTIF 37..45; /note=Effector region; /evidence=ECO:0000250 |
| Gene Encoded By | |
| Mass | 23,490 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:19669; RHEA:19670 |
| Cross Reference Brenda |