Ran GTPase-activating protein 1 (RANGAP1)
The protein contains 587 amino acids for an estimated molecular weight of 63542 Da.
GTPase activator for RAN (PubMed:8146159, PubMed:8896452, PubMed:16428860). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:8896452, PubMed:27160050). Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050). (updated: March 28, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs2229752 |
Biological Process
Activation of GTPase activity
Cellular response to vasopressin
Mitotic cell cycle
Mitotic nuclear membrane reassembly
Mitotic spindle organization
Negative regulation of protein export from nucleus
Protein sumoylation
Response to axon injury
Signal transduction
Sister chromatid cohesion
Cellular Component
Aggresome
Axon cytoplasm
Condensed chromosome kinetochore
Cytoplasm
Cytoplasmic periphery of the nuclear pore complex
Cytosol
Dendrite
Intracellular membrane-bounded organelle
Mitotic spindle
Nuclear envelope
Nuclear membrane
Nuclear pore
Nuclear pore cytoplasmic filaments
Nucleoplasm
Perinuclear region of cytoplasm
Spindle pole
The reference OMIM entry for this protein is 602362
Gtpase-activating protein, ran, 1; rangap1
Ran gtpase-activating protein 1
CLONING
RAS-related small GTP-binding proteins (GTPBPs), such as RAN (601179), participate in various intracellular signal transduction pathways. The GTP-bound form usually represents the active signaling form of the protein. Hydrolysis of GTP to GDP and phosphate occurs upon activation of a latent GTPase activity in the GTPBP and returns it to its inactive, GDP-bound state. This latent GTPase activity is induced upon interaction of GTP-bound GTPBPs with GTPase-activating proteins (GAPs). Bischoff et al. (1994) purified a GAP from a HeLa cell extract. The protein, designated RanGAP1, is a homodimeric 65-kD polypeptide. RanGAP1 specifically induced the GTPase activity of RAN, but not of RAS (190020), by over 1,000-fold. Bischoff et al. (1994) believed RanGAP1 to be the immediate antagonist of RCC1 (179710), a regulator molecule that keeps RAN in the active, GTP-bound state. Bischoff et al. (1995) purified the 65-kD RanGAP1 protein from human HeLa cells. Using PCR with degenerate primers based on RanGAP1 peptide sequences, they cloned the corresponding cDNA from a HeLa cell library. The RANGAP1 gene encodes a 587-amino acid polypeptide. The sequence is unrelated to that of GTPase activators for other RAS-related proteins, but is 88% identical to Fug1, the murine homolog of yeast Rna1p. Bischoff et al. (1995) proposed that RanGAP1 and RCC1 control RAN-dependent transport between the nucleus and cytoplasm.GENE FUNCTION
RAN is a nuclear RAS-like GTPase that is required for the bidirectional transport of proteins and ribonucleoproteins across the nuclear pore complex (NPC). RanGAP1 is a key regulator of the RAN GTP/GDP cycle. Matunis et al. (1996) reported the identification and localization of a novel form of RanGAP1. They showed that the 70-kD unmodified form of RanGAP1 is exclusively cytoplasmic, whereas the 90-kD modified form is associated with the cytoplasmic fibers of the NPC. The modified form also appeared to associate with the mitotic spindle apparatus during mitosis. These findings had specific implications for RAN function and broad implications for protein regulation by ubiquitin-like modifications. RANGAP1 is modified by the conjugation of SUMO1 (601912), and this modification is required for association of RANGAP1 with the nuclear pore complex. Okuma et al. (1999) showed that human SUA1 (SAE1; 613294), UBA2 (613295), and UBC9 (UBE2I; 601661) catalyzed in vitro sumoylation of RANGAP1 in a 2-step reaction.BIOCHEMICAL FEATURES
- Crystal Structure Seewald et al. (2002) presented the 3-dimensional structure of a Ran-RanBP1-RanGAP ternary complex in the ground state and in a transition-state mimic. The structure and biochemical experiments showed that RanGAP does not act through an arginine finger, that the basic machinery for fast GTP hydrolysis is provided exclusively by Ran, and that correct positioning of the catalytic glutamine is essential for catalysis. Bernier-Villamor et al. (2002) performed crystallographic analysis of a complex between mammalian UBC9 and a C-terminal domain of RANGAP1 at 2.5 angstroms. These experiments revealed structural determinants for recognition of consensus SUMO modification sequences found within SUMO-conjugated proteins. Structure-based mutagenesis and biochemical analysis of UBC9 and RANGAP1 revealed distinct motifs required for substrate binding and SUMO modification of p53 (191170), NFKBIA (164008), and RANGAP1. Reverter and Lima (2005) described the 3.0-angst ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602362 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed