GTP-binding nuclear protein Ran (RAN)
The protein contains 216 amino acids for an estimated molecular weight of 24423 Da.
GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs (PubMed:10400640, PubMed:8276887, PubMed:8896452, PubMed:8636225, PubMed:8692944, PubMed:9351834, PubMed:9428644, PubMed:9822603, PubMed:17209048, PubMed:26272610). Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis (PubMed:7819259, PubMed:8896452, PubMed:8636225, PubMed:8692944, PubMed:9351834, PubMed:9428644, PubMed:9822603, PubMed:29040603, PubMed:11336674, PubMed:26272610). Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport (PubMed:8896452, PubMed:9351834, PubMed:9428644). Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins (PubMed:20485264). RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation (PubMed:10408446, PubMed:29040603). Required for normal progress through mitosis (PubMed:8421051, PubMed:12194828, PubMed:29040603). The complex with BIRC5/survivin plays a role (updated: Oct. 7, 2020)
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.
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.
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| Variant | Description |
|---|---|
| dbSNP:rs11546488 |
Biological Process
Actin cytoskeleton organization
Androgen receptor signaling pathway
Cell division
Cellular protein-containing complex localization
Cellular response to mineralocorticoid stimulus
DNA metabolic process
Gene expression
GTP metabolic process
Hippocampus development
Intracellular transport of virus
MiRNA metabolic process
Mitotic cell cycle
Mitotic nuclear division
Mitotic nuclear membrane reassembly
Mitotic sister chromatid segregation
Mitotic spindle organization
Obsolete protein import into nucleus, translocation
Positive regulation of protein binding
Positive regulation of protein import into nucleus
Positive regulation of transcription, DNA-templated
Pre-miRNA export from nucleus
Protein export from nucleus
Protein import into nucleus
Protein localization to nucleolus
Regulation of cholesterol biosynthetic process
Regulation of gene silencing by miRNA
Ribosomal large subunit export from nucleus
Ribosomal small subunit export from nucleus
Ribosomal subunit export from nucleus
Signal transduction
Small GTPase mediated signal transduction
Small molecule metabolic process
SnRNA import into nucleus
Spermatid development
TRNA export from nucleus
Viral life cycle
Viral process
Cellular Component
Centriole
Cytoplasm
Cytosol
Extracellular exosome
Extracellular matrix
Host cell
Male germ cell nucleus
Manchette
Melanosome
Membrane
Midbody
Nuclear envelope
Nuclear pore
Nucleolus
Nucleoplasm
Nucleus
Protein complex
Protein-containing complex
Recycling endosome
RNA nuclear export complex
Sperm flagellum
Molecular Function
Androgen receptor binding
Cadherin binding
Chromatin binding
Dynein intermediate chain binding
GDP binding
GTP binding
GTPase activity
Importin-alpha family protein binding
Magnesium ion binding
Poly(A) RNA binding
Protein complex binding
Protein domain specific binding
Protein heterodimerization activity
Protein-containing complex binding
RNA binding
Transcription coactivator activity
The reference OMIM entry for this protein is 601179
Ras-related nuclear protein; ran
CLONING
RAN (Ras-related nuclear protein) is a small GTP-binding protein belonging to the RAS superfamily (see 190020) that is essential for the translocation of RNA and proteins through the nuclear pore complex (Ren et al., 1993). The RAN protein is also involved in control of DNA synthesis and of cell cycle progression. By screening a human teratocarcinoma cDNA library with a mixed-oligonucleotide probe corresponding to a domain conserved among RAS-like proteins, Drivas et al. (1990) identified a cDNA, TC4, identical to RAN. Ren et al. (1993) showed that nuclear localization of RAN requires the presence of RCC1 (179710) and that mutations in RAN expected to disrupt GTP hydrolysis led to a disruption of DNA synthesis. Because of its many functions, it is likely that RAN interacts with several other proteins (see 601180 and 601181). Coutavas et al. (1994) showed that 2 distinct, but closely related, Ran transcripts from separate loci are present in the mouse, 1 of which is specific to the testis.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. To provide a basis for understanding the crucial cargo-release step of nuclear import, Lee et al. (2005) presented the crystal structure of full-length yeast importin-beta (Kap95; see 602738) complexed with RanGTP. They identified a key interaction site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95. This interaction produced a change in helicoidal pitch that locks Kap95 in a conformation that cannot bind importin-alpha (see 600685) or cargo. Lee et al. (2005) suggested an allosteric mechanism for nuclear import complex disassembly by RanGTP. Monecke et al. (2009) presented the crystal structure of the snurportin-1 (SPN1; 607902)-CRM1 (602559)-RanGTP export complex at 2.5-angstrom resolution. SPN1 is a nuclear import adapter for cytoplasmically assembled, m3G (5-prime-2,2,7-terminal trimethylguanosine)-capped spliceosomal U snRNPs. The structure showed how CRM1 can specifically return the cargo-free form of SPN1 to the cytoplasm. The extensive contact area includes 5 hydrophobic residues at the SPN1 amino terminus that dock into a hydrophobic cleft of CRM1, as well as numerous hydrophilic contacts of CRM1 to m3G cap-binding domain and carboxyl-terminal residues of SPN1. Monecke et al. (2009) concluded that RanGTP promotes cargo binding to CRM1 solely through long-range conformational changes in the exportin.GENE FUNCTION
Ohba et al. (1999) demonstrated that the nucleotide exchange activity of RCC1, the only known nucleotide exchange factor for RAN, was required for microtubule aster formation with or without demembranated sperm in Xenopus egg extracts arrested in meiosis II. In the RCC1-depleted egg extracts, RanGTP (see RANGAP1, 602362), but not RanGDP, induced self-organization of microtubule asters, and the process required the activity of dynein (see 603297). Thus, RAN was shown to regulate formation of the microtubule network. The egg extracts used in the experiments by Ohba et al. (1999) were prepared from unfertilized eggs ar ... More on the omim web site
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601179 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed