P46061 · RAGP1_MOUSE
- ProteinRan GTPase-activating protein 1
- GeneRangap1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids589 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
GTPase activator for RAN. Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:18305100).
Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (By similarity).
Required for postimplantation embryonic development (PubMed:8314081).
Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (By similarity).
Required for postimplantation embryonic development (PubMed:8314081).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 564 | Hydrophobic interaction with UBE2I | ||||
Sequence: F | ||||||
Site | 567 | Hydrophobic interaction with UBE2I | ||||
Sequence: K |
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 | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRan GTPase-activating protein 1
- Short namesRanGAP1
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP46061
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Cytoplasmic during interphase (PubMed:26506250).
Detected at the nuclear envelope during interphase (PubMed:26506250, PubMed:9442102, PubMed:9456312).
Shuttles between nucleus and cytoplasm (PubMed:26506250).
Targeted to the nuclear pores after sumoylation. During mitosis, associates with mitotic spindles, but is essentially not detected at the spindle poles. Association with kinetochores appears soon after nuclear envelope breakdown and persists until late anaphase. Mitotic location also requires sumoylation (By similarity).
Detected at the nuclear envelope during interphase (PubMed:26506250, PubMed:9442102, PubMed:9456312).
Shuttles between nucleus and cytoplasm (PubMed:26506250).
Targeted to the nuclear pores after sumoylation. During mitosis, associates with mitotic spindles, but is essentially not detected at the spindle poles. Association with kinetochores appears soon after nuclear envelope breakdown and persists until late anaphase. Mitotic location also requires sumoylation (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Embryonic development is arrested around 6 dpc.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 411 | Greatly reduced phosphorylation by CDK1 or CDK2. Completely abolished phosphorylation by CDK1 or CDK2; when associated with D-444. | ||||
Sequence: T → D | ||||||
Mutagenesis | 444 | Little change in phosphorylation by CDK1 or CDK2. Completely abolished phosphorylation by CDK1 or CDK2; when associated with D-411. | ||||
Sequence: S → D | ||||||
Mutagenesis | 512 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: N → A | ||||||
Mutagenesis | 516 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: T → A | ||||||
Mutagenesis | 517 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: R → A | ||||||
Mutagenesis | 520 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: I → A | ||||||
Mutagenesis | 521 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: H → A | ||||||
Mutagenesis | 522 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: M → A | ||||||
Mutagenesis | 524 | No sumoylation. | ||||
Sequence: L → A | ||||||
Mutagenesis | 525 | Disrupted binding to UBE2I, and no sumoylation. | ||||
Sequence: L → A | ||||||
Mutagenesis | 526 | No UBE2I binding nor sumoylation. | ||||
Sequence: K → A | ||||||
Mutagenesis | 526 | Absence of sumoylation. Not targeted to the nuclear envelope rim nor to nuclear pore complexes. Disrupted sumoylation. No interaction with SUMO1; when associated with A-564 and with or without SUMO1 A-97. | ||||
Sequence: K → R | ||||||
Mutagenesis | 528 | No UBE2I binding nor sumoylation. | ||||
Sequence: E → A | ||||||
Mutagenesis | 529 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: D → A | ||||||
Mutagenesis | 531 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: I → A | ||||||
Mutagenesis | 537 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: L → A | ||||||
Mutagenesis | 541-589 | Abolishes accumulation in the nucleus. | ||||
Sequence: Missing | ||||||
Mutagenesis | 560 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: L → A | ||||||
Mutagenesis | 563 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: A → L | ||||||
Mutagenesis | 564 | No UBE2I binding nor sumoylation. Not targeted to nuclear pore complexes; when associated with R-526. | ||||
Sequence: F → A | ||||||
Mutagenesis | 567 | No UBE2I binding nor sumoylation. | ||||
Sequence: K → A | ||||||
Mutagenesis | 567-589 | No effect on accumulation in the nucleus. | ||||
Sequence: Missing | ||||||
Mutagenesis | 569 | No effect on UBE2I binding nor on sumoylation. | ||||
Sequence: N → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 29 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000056738 | 2-589 | Ran GTPase-activating protein 1 | |||
Sequence: ASEDIAKLAETLAKTQVAGGQLSFKGKGLKLNTAEDAKDVIKEIEEFDGLEALRLEGNTVGVEAARVIAKALEKKSELKRCHWSDMFTGRLRSEIPPALISLGEGLITAGAQLVELDLSDNAFGPDGVRGFEALLKSPACFTLQELKLNNCGMGIGGGKILAAALTECHRKSSAQGKPLALKVFVAGRNRLENDGATALAEAFGIIGTLEEVHMPQNGINHPGVTALAQAFAINPLLRVINLNDNTFTEKGGVAMAETLKTLRQVEVINFGDCLVRSKGAVAIADAVRGGLPKLKELNLSFCEIKRDAALVVAEAVADKAELEKLDLNGNALGEEGCEQLQEVMDSFNMAKVLASLSDDEGEDEDEEEEGEEDDEEEEDEEDEEDDDEEEEEQEEEEEPPQRGSGEEPATPSRKILDPNSGEPAPVLSSPTPTDLSTFLSFPSPEKLLRLGPKVSVLIVQQTDTSDPEKVVSAFLKVASVFRDDASVKTAVLDAIDALMKKAFSCSSFNSNTFLTRLLIHMGLLKSEDKIKAIPSLHGPLMVLNHVVRQDYFPKALAPLLLAFVTKPNGALETCSFARHNLLQTLYNI | ||||||
Cross-link | 8 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | ||||||
Cross-link | 8 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate | ||||
Sequence: K | ||||||
Cross-link | 8 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Cross-link | 15 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 24 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 279 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 301 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 358 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 411 | Phosphothreonine; by CDK2 | ||||
Sequence: T | ||||||
Modified residue | 430 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 437 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 438 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 441 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 444 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 454 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 526 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Cross-link | 526 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | ||||||
Cross-link | 526 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate | ||||
Sequence: K | ||||||
Cross-link | 526 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K |
Post-translational modification
Phosphorylation occurs before nuclear envelope breakdown and continues throughout mitosis. Phosphorylated by the M-phase kinase cyclin B/Cdk1, in vitro. Differential timimg of dephosphorylation occurs during phases of mitosis. The phosphorylated form remains associated with RANBP2/NUP358 and the SUMO E2-conjugating enzyme, UBE2I, on nuclear pore complex (NPC) diassembly and during mitosis.
Sumoylated (PubMed:11853669, PubMed:26506250).
Sumoylation is necessary for targeting to the nuclear envelope (NE) (PubMed:16469311).
Sumoylation is necessary for association with mitotic spindles and kinetochores during mitosis (By similarity).
Also required for interaction with RANBP2 and is mediated by UBE2I (PubMed:11853669, PubMed:9456312).
Desumoylated by HINT1 (PubMed:31088288).
Sumoylation is necessary for targeting to the nuclear envelope (NE) (PubMed:16469311).
Sumoylation is necessary for association with mitotic spindles and kinetochores during mitosis (By similarity).
Also required for interaction with RANBP2 and is mediated by UBE2I (PubMed:11853669, PubMed:9456312).
Desumoylated by HINT1 (PubMed:31088288).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in adult brain, liver, kidney, intestine, uterus and ovary.
Developmental stage
Detected in embryos at 7.5 dpc, but not at 6 dpc.
Gene expression databases
Interaction
Subunit
Homodimer (PubMed:7891706).
Interacts with RAN (PubMed:7891706).
Forms a complex with RANBP2/NUP358, NXF1 and NXT1 (By similarity).
Forms a tight complex in association with RANBP2 and UBE2I/UBC9, the ubiquitin-conjugating enzyme E2 (PubMed:11853669).
Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2 (PubMed:11853669, PubMed:18305100, PubMed:9456312).
The complex composed of RANBP2, SUMO1, RANGAP1 and UBE2I associates with nuclear pore complexes (By similarity).
Identified in a complex composed of RAN, RANBP2, sumoylated RANGAP1, UBE2I and XPO1 (By similarity).
Interacts with TRAF6 (By similarity).
Interacts with SUMO1 and SENP1 (By similarity).
Interacts (when sumoylated) with MYCBP2; interaction inhibits MYCBP2 E3 ubiquitin-protein ligase activity and promotes MYCBP2 translocation to the nucleus (PubMed:26304119).
Interacts with RAN (PubMed:7891706).
Forms a complex with RANBP2/NUP358, NXF1 and NXT1 (By similarity).
Forms a tight complex in association with RANBP2 and UBE2I/UBC9, the ubiquitin-conjugating enzyme E2 (PubMed:11853669).
Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2 (PubMed:11853669, PubMed:18305100, PubMed:9456312).
The complex composed of RANBP2, SUMO1, RANGAP1 and UBE2I associates with nuclear pore complexes (By similarity).
Identified in a complex composed of RAN, RANBP2, sumoylated RANGAP1, UBE2I and XPO1 (By similarity).
Interacts with TRAF6 (By similarity).
Interacts with SUMO1 and SENP1 (By similarity).
Interacts (when sumoylated) with MYCBP2; interaction inhibits MYCBP2 E3 ubiquitin-protein ligase activity and promotes MYCBP2 translocation to the nucleus (PubMed:26304119).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat, region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 48-71 | LRR 1 | ||||
Sequence: FDGLEALRLEGNTVGVEAARVIAK | ||||||
Repeat | 111-134 | LRR 2 | ||||
Sequence: GAQLVELDLSDNAFGPDGVRGFEA | ||||||
Repeat | 207-230 | LRR 3 | ||||
Sequence: IGTLEEVHMPQNGINHPGVTALAQ | ||||||
Repeat | 235-258 | LRR 4 | ||||
Sequence: NPLLRVINLNDNTFTEKGGVAMAE | ||||||
Repeat | 292-315 | LRR 5 | ||||
Sequence: LPKLKELNLSFCEIKRDAALVVAE | ||||||
Repeat | 320-343 | LRR 6 | ||||
Sequence: KAELEKLDLNGNALGEEGCEQLQE | ||||||
Region | 357-436 | Disordered | ||||
Sequence: LSDDEGEDEDEEEEGEEDDEEEEDEEDEEDDDEEEEEQEEEEEPPQRGSGEEPATPSRKILDPNSGEPAPVLSSPTPTDL | ||||||
Compositional bias | 359-402 | Acidic residues | ||||
Sequence: DDEGEDEDEEEEGEEDDEEEEDEEDEEDDDEEEEEQEEEEEPPQ | ||||||
Motif | 525-528 | SUMO conjugation | ||||
Sequence: LKSE | ||||||
Region | 541-566 | Important for accumulation in the nucleus | ||||
Sequence: LMVLNHVVRQDYFPKALAPLLLAFVT |
Sequence similarities
Belongs to the RNA1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length589
- Mass (Da)63,531
- Last updated2011-07-27 v2
- Checksum775ADE3A53EFD558
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8VHK9 | A0A2R8VHK9_MOUSE | Rangap1 | 257 | ||
A0A2R8W753 | A0A2R8W753_MOUSE | Rangap1 | 144 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 181 | in Ref. 1; AAA17681 | ||||
Sequence: A → R | ||||||
Compositional bias | 359-402 | Acidic residues | ||||
Sequence: DDEGEDEDEEEEGEEDDEEEEDEEDEEDDDEEEEEQEEEEEPPQ | ||||||
Sequence conflict | 413 | in Ref. 2; AAB60517 | ||||
Sequence: S → L |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U08110 EMBL· GenBank· DDBJ | AAA17681.1 EMBL· GenBank· DDBJ | mRNA | ||
U20857 EMBL· GenBank· DDBJ | AAB60517.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AK146670 EMBL· GenBank· DDBJ | BAE27347.1 EMBL· GenBank· DDBJ | mRNA | ||
AK159009 EMBL· GenBank· DDBJ | BAE34767.1 EMBL· GenBank· DDBJ | mRNA | ||
AK159525 EMBL· GenBank· DDBJ | BAE35154.1 EMBL· GenBank· DDBJ | mRNA | ||
BC066213 EMBL· GenBank· DDBJ | AAH66213.1 EMBL· GenBank· DDBJ | mRNA | ||
BC071200 EMBL· GenBank· DDBJ | AAH71200.1 EMBL· GenBank· DDBJ | mRNA |