Tether containing UBX domain for GLUT4 (ASPSCR1)
The protein contains 553 amino acids for an estimated molecular weight of 60183 Da.
Tethering protein that sequesters GLUT4-containing vesicles in the cytoplasm in the absence of insulin. Modulates the amount of GLUT4 that is available at the cell surface (By similarity). Enhances VCP methylation catalyzed by VCPKMT. (updated: March 4, 2015)
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.
- 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.
- 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.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs8074498 | |
| dbSNP:rs34085048 | |
| dbSNP:rs13087 |
Biological Process
Glucose homeostasis
Intracellular protein transport
Membrane organization
Positive regulation of protein modification process
Regulation of glucose import
Cellular Component
Cytoplasmic side of plasma membrane
Cytosol
Endomembrane system
Endoplasmic reticulum-Golgi intermediate compartment membrane
Extrinsic component of membrane
Intracellular membrane-bounded organelle
Nucleoplasm
Perinuclear region of cytoplasm
Plasma membrane
Vesicle membrane
Molecular Function
The reference OMIM entry for this protein is 606236
Alveolar soft part sarcoma chromosome region, candidate 1; aspscr1
Aspl
Tether, containing ubx domain for glut4; tug aspscr1/tfe3 fusion gene, included
CLONING
Cytogenetic studies identified a recurrent der(17) due to a nonreciprocal t(X;17)(p11.2;q25) in cases of alveolar soft-part sarcoma (ASPS; 606243) (Joyama et al., 1999). By Southern blot analysis using a TFE3 (314310) probe, Ladanyi et al. (2001) identified nongermline bands in several ASPS cases, consistent with rearrangement and possible fusion of TFE3 with a gene on 17q25. By amplification of the 5-prime portion of cDNAs containing the 3-prime portion of TFE3 in 2 ASPS cases, they identified a novel sequence, ASPSCR1 (designated ASPL by the authors), fused in-frame to TFE3 exon 4 or exon 3. RT-PCR analysis detected an ASPSCR1/TFE3 fusion transcript in all 12 ASPS cases studied. The ASPSCR1/TFE3 fusion replaces the N-terminal portion of TFE3 by the fused ASPSCR1 sequences, while retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of ASPS. Ladanyi et al. (2001) identified major and minor splice forms of the ASPSCR1 transcript which differ by the absence or presence of a 47-nucleotide segment from exon 2, which encodes part of the 5-prime untranslated portion of ASPSCR1. They determined that the ASPSCR1 cDNA encodes a deduced 476-amino acid protein containing a UBX-like domain in its C terminus. Northern blot analysis detected a predominant 1.9-kb transcript in all tissues tested, with highest expression in heart, skeletal muscle, pancreas, and testis. Expression in fetal tissues appeared notably lower than in adult tissues. ASPSCR1 expression was also found in all cancer cell lines tested. Independently, Heimann et al. (2001) identified the ASPSCR1 gene, which they called RCC17, partnered with TFE3 in two 5-year-old Belgian girls of African origin in whom papillary renal cell carcinomas (300854) carried the translocation t(X;17)(p11.2;q25). In both patients, the t(X;17) fused the N terminal region of RCC17 to the C terminal region of TFE3 including the bHLH DNA-binding domain and the leucine zipper dimerization domain. The reciprocal fusion transcript TFE3/RCC17 was also expressed. Cloutier et al. (2013) stated that the deduced 553-amino acid ASPSCR1 protein contains 2 N-terminal ubiquitin-like domains, followed by an SHP box, a coiled-coil region, and a ubiquitin regulatory X domain.GENE FUNCTION
Insulin (176730) stimulates glucose uptake in fat and muscle by mobilizing the GLUT4 glucose transporter (138190). GLUT4 is sequestered intracellularly in the absence of insulin, and is redistributed to the plasma membrane within minutes of insulin stimulation. Bogan et al. (2003) described a functional screen to identify proteins that modulate GLUT4 distribution, and identified TUG as a putative tether, containing a UBX domain, for GLUT4. They identified the ASPL protein as the probable human homolog of murine TUG. In truncated form, TUG acts in a dominant-negative manner to inhibit insulin-stimulated GLUT4 redistribution in Chinese hamster ovary cells and 3T3-L1 adipocytes. Full-length TUG forms a complex specifically with GLUT4; in 3T3-L1 adipocytes, this complex is present in unstimulated cells and is largely disassembled by insulin. Endogenous TUG is localized with the insulin-mobilizable pool of GLUT4 in unstimulated 3T3-L1 adipocytes, and is not mobilized to the plasma membrane by insulin. Distinct regions of TUG are required to bind GLUT4 and to retain GLUT4 intracellularly in transfected, nonadipose cells. Bogan et al. (2003) concluded that TUG traps endoc ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 606236 was added.