Importin-11 (IPO11)

The protein contains 975 amino acids for an estimated molecular weight of 112535 Da.

 

Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Mediates the nuclear import of UBE2E3, and of RPL12 (By similarity). (updated: Feb. 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 0%
Model score: 35

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VariantDescription
dbSNP:rs35107530
dbSNP:rs11544795

The reference OMIM entry for this protein is 610889

Importin 11; ipo11
Ran-binding protein 11; ranbp11 synleurin, included; slrn, included

DESCRIPTION

Importins, including IPO11, are a members of the karyopherin/importin-beta family of transport receptors (see KPNB1; 602738) that mediate nucleocytoplasmic transport of protein and RNA cargoes (Plafker and Macara, 2000).

CLONING

By database analysis using S. cerevisiae Lph2 as probe, followed by 5-prime RACE of a human brain cDNA library, Plafker and Macara (2000) cloned IPO11. The deduced 975-amino acid protein shares 24% amino acid identity with S. cerevisiae Lph2 protein. Northern blot analysis detected a 4.4-kb transcript in all human tissues examined. Immunofluorescence studies localized IPO11 to the nucleus in baby hamster kidney (BHK) cells. Wang et al. (2003) isolated a splice variant of IPO11, which they called synleurin, by screening for Toll-like receptor homologs in a human cDNA database. The deduced 623-amino acid variant contains a transmembrane domain and 12 leucine-rich repeats over the extracellular domain. Northern blot analysis detected a 2.5-kb transcript in human spleen, thymus, prostate, testis, small intestine, colon, and peripheral blood leukocytes, with 2 additional 4.3- and 5.0-kb bands in testis.

GENE FUNCTION

Using yeast 2-hybrid and in vitro immunoprecipitation studies, Plafker and Macara (2000) showed that IPO11 binds Ran GTPase (RAN; 601179) in its GTP-bound form. Deletion analysis showed that N-terminal region of IPO11 contains the RAN-binding domain. Using a heterokaryon shuttling assay with BHK cells fused with a transformed HeLa cell line, they demonstrated that IPO11 shuttles between the donor and acceptor nuclei of the fused cells, suggesting that IPO11 shuttles constitutively between the nuclear and cytoplasmic compartments. Yeast 2-hybrid and GST pull-down analysis showed that IPO11 interacts specifically with mouse E2-type ubiquitin conjugating enzyme UbcM2 (UBE2E3; 604151). The IPO11-UbcM2 complex was disrupted by GTP-bound Ran, consistent with the model that transport receptor-cargo complexes form in the cytoplasm and are dissociated by Ran-GTP in the nucleus. Using yeast 2-hybrid and GST pull-down studies, Plafker and Macara (2002) showed that IPO11 binds RPL12 (180475). Competition assay and microinjection studies in BHK cells showed that RPL12 and UbcM2 interact with the same or overlapping sites on IPO11, competing with each other for IPO11 binding. IPO11 increased nuclear accumulation of RPL12 in a RAN-dependent manner, and overexpression of an IPO11 mutant lacking the RAN-binding domain did not increase nuclear accumulation of RPL12. In vitro binding assay showed that IPO11 did not bind RPL23A (602326), and transient transfection assay showed that importin-beta and IPO5 (RANBP5; 602008) had no effect on nucleocytoplasmic distribution of RPL12, indicating that IPO11 is a specific nuclear import receptor for RPL12. Wang et al. (2003) found that synleurin plays a role in potentiation of cytokine responses by amplifying signal transduction activation of FGF2 (134920), EGF (131530), PDGFB (190040), IGF1 (147440), IGF2 (147470), and lipopolysaccharide when expressed in HEK293 cells.

MAPPING

By genomic sequence analysis, Wang et al. (2003) mapped the IPO11 gene to chromosome 5q12.1 ... More on the omim web site

Subscribe to this protein entry history

Dec. 10, 2018: Protein entry updated
Automatic update: model status changed

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 610889 was added.