P46060 · RAGP1_HUMAN
- ProteinRan GTPase-activating protein 1
- GeneRANGAP1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids587 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
GTPase activator for RAN (PubMed:16428860, PubMed:8146159, PubMed:8896452).
Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:27160050, PubMed:8896452).
Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050).
Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:27160050, PubMed:8896452).
Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 562 | Hydrophobic interaction with UBE2I | ||||
Sequence: F | ||||||
Site | 565 | 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 | |||
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Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameRan GTPase-activating protein 1
- Short namesRanGAP1
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP46060
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Cytoplasmic during interphase. Detected at the nuclear envelope during interphase (PubMed:11854305, PubMed:15037602).
Targeted to the nuclear pores after sumoylation (PubMed:11854305).
During mitosis, associates with mitotic spindles, but is essentially not detected at the spindle poles (PubMed:11854305, PubMed:15037602).
Association with kinetochores appears soon after nuclear envelope breakdown and persists until late anaphase (PubMed:11854305).
Mitotic location also requires sumoylation (PubMed:11854305).
Targeted to the nuclear pores after sumoylation (PubMed:11854305).
During mitosis, associates with mitotic spindles, but is essentially not detected at the spindle poles (PubMed:11854305, PubMed:15037602).
Association with kinetochores appears soon after nuclear envelope breakdown and persists until late anaphase (PubMed:11854305).
Mitotic location also requires sumoylation (PubMed:11854305).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 91 | Abolishes RANGTPase activation. | ||||
Sequence: R → A | ||||||
Natural variant | VAR_029240 | 133 | in dbSNP:rs2229752 | |||
Sequence: E → Q | ||||||
Mutagenesis | 356 | No effect on phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 358 | Strongly decreased phosphorylation. No effect on sumoylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 524 | Loss of cross-link to SUMO1. Abolishes association with nuclear pores during interphase, and with mitotic spindles during mitosis. | ||||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 656 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000056737 | 2-587 | UniProt | Ran GTPase-activating protein 1 | |||
Sequence: ASEDIAKLAETLAKTQVAGGQLSFKGKSLKLNTAEDAKDVIKEIEDFDSLEALRLEGNTVGVEAARVIAKALEKKSELKRCHWSDMFTGRLRTEIPPALISLGEGLITAGAQLVELDLSDNAFGPDGVQGFEALLKSSACFTLQELKLNNCGMGIGGGKILAAALTECHRKSSAQGKPLALKVFVAGRNRLENDGATALAEAFRVIGTLEEVHMPQNGINHPGITALAQAFAVNPLLRVINLNDNTFTEKGAVAMAETLKTLRQVEVINFGDCLVRSKGAVAIADAIRGGLPKLKELNLSFCEIKRDAALAVAEAMADKAELEKLDLNGNTLGEEGCEQLQEVLEGFNMAKVLASLSDDEDEEEEEEGEEEEEEAEEEEEEDEEEEEEEEEEEEEEPQQRGQGEKSATPSRKILDPNTGEPAPVLSSPPPADVSTFLAFPSPEKLLRLGPKSSVLIAQQTDTSDPEKVVSAFLKVSSVFKDEATVRMAVQDAVDALMQKAFNSSSFNSNTFLTRLLVHMGLLKSEDKVKAIANLYGPLMALNHMVQQDYFPKALAPLLLAFVTKPNSALESCSFARHSLLQTLYKV | |||||||
Cross-link | 8 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate | ||||
Sequence: K | |||||||
Cross-link | 8 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | |||||||
Cross-link | 15 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue | 24 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 24 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 279 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue | 301 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 301 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 358 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 409 | UniProt | Phosphothreonine; by CDK2 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 427 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 428 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 428 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 435 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 435 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 436 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 436 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 442 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 442 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 452 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 506 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 524 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Cross-link | 524 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate | ||||
Sequence: K | |||||||
Cross-link | 524 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 572 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 586 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
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:11854305, PubMed:15037602, PubMed:26304119, PubMed:27160050).
Sumoylation is necessary for targeting to the nuclear envelope (NE), and for association with mitotic spindles and kinetochores during mitosis (PubMed:11854305).
Also required for interaction with RANBP2 and is mediated by UBE2I (PubMed:27160050).
Desumoylated by HINT1 (By similarity).
Sumoylation is necessary for targeting to the nuclear envelope (NE), and for association with mitotic spindles and kinetochores during mitosis (PubMed:11854305).
Also required for interaction with RANBP2 and is mediated by UBE2I (PubMed:27160050).
Desumoylated by HINT1 (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in brain, thymus and testis.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (PubMed:8146159).
Interacts with RAN (PubMed:16428860, PubMed:7891706, PubMed:8896452).
Forms a complex with RANBP2/NUP358, NXF1 and NXT1 (PubMed:14729961).
Forms a tight complex in association with RANBP2/NUP358 and UBE2I/UBC9, the ubiquitin-conjugating enzyme E2 (PubMed:15037602, PubMed:15931224, PubMed:22194619, PubMed:27160050).
Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2/NUP358 (PubMed:15037602, PubMed:15931224, PubMed:27160050).
The complex composed of RANBP2, SUMO1, RANGAP1 and UBE2I associates with nuclear pore complexes (PubMed:15037602, PubMed:15931224).
Identified in a complex composed of RAN, RANBP2, sumoylated RANGAP1, UBE2I and XPO1 (PubMed:27160050).
Identified in a complex composed of RAN, RANGAP1 and RANBP1 (PubMed:16428860).
Interacts with TRAF6 (PubMed:18093978).
Interacts with SUMO1 and SENP1 (PubMed:17099698).
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:16428860, PubMed:7891706, PubMed:8896452).
Forms a complex with RANBP2/NUP358, NXF1 and NXT1 (PubMed:14729961).
Forms a tight complex in association with RANBP2/NUP358 and UBE2I/UBC9, the ubiquitin-conjugating enzyme E2 (PubMed:15037602, PubMed:15931224, PubMed:22194619, PubMed:27160050).
Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2/NUP358 (PubMed:15037602, PubMed:15931224, PubMed:27160050).
The complex composed of RANBP2, SUMO1, RANGAP1 and UBE2I associates with nuclear pore complexes (PubMed:15037602, PubMed:15931224).
Identified in a complex composed of RAN, RANBP2, sumoylated RANGAP1, UBE2I and XPO1 (PubMed:27160050).
Identified in a complex composed of RAN, RANGAP1 and RANBP1 (PubMed:16428860).
Interacts with TRAF6 (PubMed:18093978).
Interacts with SUMO1 and SENP1 (PubMed:17099698).
Interacts (when sumoylated) with MYCBP2; interaction inhibits MYCBP2 E3 ubiquitin-protein ligase activity and promotes MYCBP2 translocation to the nucleus (PubMed:26304119).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P46060 | HTT P42858 | 10 | EBI-396091, EBI-466029 | |
BINARY | P46060 | RANBP2 P49792 | 5 | EBI-396091, EBI-973138 | |
BINARY | P46060 | SUMO1 P63165 | 14 | EBI-396091, EBI-80140 | |
BINARY | P46060 | UBE2I P63279 | 14 | EBI-396091, EBI-80168 |
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: FDSLEALRLEGNTVGVEAARVIAK | ||||||
Repeat | 111-134 | LRR 2 | ||||
Sequence: GAQLVELDLSDNAFGPDGVQGFEA | ||||||
Repeat | 207-230 | LRR 3 | ||||
Sequence: IGTLEEVHMPQNGINHPGITALAQ | ||||||
Repeat | 235-258 | LRR 4 | ||||
Sequence: NPLLRVINLNDNTFTEKGAVAMAE | ||||||
Repeat | 292-319 | LRR 5 | ||||
Sequence: LPKLKELNLSFCEIKRDAALAVAEAMAD | ||||||
Repeat | 320-343 | LRR 6 | ||||
Sequence: KAELEKLDLNGNTLGEEGCEQLQE | ||||||
Region | 357-430 | Disordered | ||||
Sequence: LSDDEDEEEEEEGEEEEEEAEEEEEEDEEEEEEEEEEEEEEPQQRGQGEKSATPSRKILDPNTGEPAPVLSSPP | ||||||
Compositional bias | 358-398 | Acidic residues | ||||
Sequence: SDDEDEEEEEEGEEEEEEAEEEEEEDEEEEEEEEEEEEEEP | ||||||
Motif | 523-526 | SUMO conjugation | ||||
Sequence: LKSE |
Sequence similarities
Belongs to the RNA1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length587
- Mass (Da)63,542
- Last updated1995-11-01 v1
- Checksum3C18068AAC06B98F
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 358-398 | Acidic residues | ||||
Sequence: SDDEDEEEEEEGEEEEEEAEEEEEEDEEEEEEEEEEEEEEP |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X82260 EMBL· GenBank· DDBJ | CAA57714.1 EMBL· GenBank· DDBJ | mRNA | ||
AB058738 EMBL· GenBank· DDBJ | BAB47464.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
CR456557 EMBL· GenBank· DDBJ | CAG30443.1 EMBL· GenBank· DDBJ | mRNA | ||
AL035681 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC014044 EMBL· GenBank· DDBJ | AAH14044.1 EMBL· GenBank· DDBJ | mRNA | ||
BC041396 EMBL· GenBank· DDBJ | AAH41396.1 EMBL· GenBank· DDBJ | mRNA |