Q6IQ22 · RAB12_HUMAN
- ProteinRas-related protein Rab-12
- GeneRAB12
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids244 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab may play a role in protein transport from recycling endosomes to lysosomes regulating, for instance, the degradation of the transferrin receptor. Involved in autophagy (By similarity).
Activity regulation
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity).
That Rab is activated by DENND3, a guanine exchange factor
That Rab is activated by DENND3, a guanine exchange factor
Features
Showing features for binding site.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | autophagosome | |
Cellular Component | cytosol | |
Cellular Component | endosome | |
Cellular Component | Golgi membrane | |
Cellular Component | lysosomal membrane | |
Cellular Component | lysosome | |
Cellular Component | plasma membrane | |
Cellular Component | recycling endosome membrane | |
Cellular Component | synaptic vesicle | |
Cellular Component | trans-Golgi network transport vesicle | |
Molecular Function | GDP binding | |
Molecular Function | GTP binding | |
Molecular Function | GTPase activity | |
Biological Process | autophagy | |
Biological Process | endocytic recycling | |
Biological Process | endosome to lysosome transport | |
Biological Process | exocytosis | |
Biological Process | protein catabolic process | |
Biological Process | protein secretion | |
Biological Process | Rab protein signal transduction |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRas-related protein Rab-12
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6IQ22
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Recycling endosome membrane ; Lipid-anchor
Lysosome membrane ; Lipid-anchor
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 106 | Loss of phosphorylation. No effect on GDI1 and GDI2 binding. | ||||
Sequence: S → A | ||||||
Mutagenesis | 106 | Phosphomimetic mutant. Loss of GDI1, GDI2, CHM and CHML binding. | ||||
Sequence: S → E |
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain, modified residue (large scale data), lipidation.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000271377 | 1-244 | UniProt | Ras-related protein Rab-12 | |||
Sequence: MDPGAALQRRAGGGGGLGAGSPALSGGQGRRRKQPPRPADFKLQVIIIGSRGVGKTSLMERFTDDTFCEACKSTVGVDFKIKTVELRGKKIRLQIWDTAGQERFNSITSAYYRSAKGIILVYDITKKETFDDLPKWMKMIDKYASEDAELLLVGNKLDCETDREITRQQGEKFAQQITGMRFCEASAKDNFNVDEIFLKLVDDILKKMPLDILRNELSNSILSLQPEPEIPPELPPPRPHVRCC | |||||||
Modified residue | 21 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 21 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 25 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 25 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 106 | UniProt | Phosphoserine; by LRRK2 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 106 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 218 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 220 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 223 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Lipidation | 243 | UniProt | S-geranylgeranyl cysteine | ||||
Sequence: C | |||||||
Lipidation | 244 | UniProt | S-geranylgeranyl cysteine | ||||
Sequence: C |
Post-translational modification
Phosphorylation of Ser-106 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with RABIF (PubMed:21194374).
Interacts with OPTN (By similarity).
Interacts with LRRK2; interaction facilitates phosphorylation of Ser-106 (PubMed:26824392).
Interacts with GDI1, GDI2, CHM and CHML; these interactions are disrupted by phosphorylation on Ser-106 (PubMed:26824392, PubMed:29125462).
Interacts with RILPL1 and RILPL2; these interactions are dependent on phosphorylation of Ser-106 (PubMed:26824392, PubMed:29125462).
Interacts with OPTN (By similarity).
Interacts with LRRK2; interaction facilitates phosphorylation of Ser-106 (PubMed:26824392).
Interacts with GDI1, GDI2, CHM and CHML; these interactions are disrupted by phosphorylation on Ser-106 (PubMed:26824392, PubMed:29125462).
Interacts with RILPL1 and RILPL2; these interactions are dependent on phosphorylation of Ser-106 (PubMed:26824392, PubMed:29125462).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q6IQ22 | LRRK2 Q5S007 | 2 | EBI-4289591, EBI-5323863 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-37 | Disordered | ||||
Sequence: MDPGAALQRRAGGGGGLGAGSPALSGGQGRRRKQPPR | ||||||
Motif | 71-79 | Effector region | ||||
Sequence: CKSTVGVDF | ||||||
Region | 225-244 | Disordered | ||||
Sequence: QPEPEIPPELPPPRPHVRCC |
Sequence similarities
Belongs to the small GTPase superfamily. Rab family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length244
- Mass (Da)27,248
- Last updated2007-01-09 v3
- ChecksumB4DC65DD0DCB45C4
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3B3ITT1 | A0A3B3ITT1_HUMAN | RAB12 | 340 |
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AP001793 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471113 EMBL· GenBank· DDBJ | EAX01616.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC050338 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
BC071600 EMBL· GenBank· DDBJ | AAH71600.2 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
BC098407 EMBL· GenBank· DDBJ | AAH98407.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. |