Serine-threonine kinase receptor-associated protein (STRAP)
The protein contains 350 amino acids for an estimated molecular weight of 38438 Da.
The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein. (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.
- 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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Biological Process
Alternative mRNA splicing, via spliceosome
Maintenance of gastrointestinal epithelium
Negative regulation of epithelial cell migration
Negative regulation of epithelial cell proliferation
Negative regulation of epithelial to mesenchymal transition
Negative regulation of pathway-restricted SMAD protein phosphorylation
Negative regulation of transcription by RNA polymerase II
Negative regulation of transforming growth factor beta receptor signaling pathway
Neuron differentiation
Spliceosomal snRNP assembly
Transforming growth factor beta receptor signaling pathway
Cellular Component
Cytoplasm
Cytosol
Nucleoplasm
Nucleus
Plasma membrane
SMN complex
SMN-Sm protein complex
Molecular Function
MRNA binding
Poly(A) RNA binding
RNA binding
Signaling receptor binding
U2 snRNP binding
The reference OMIM entry for this protein is 605986
Serine/threonine kinase receptor-associated protein; strap
Unr-interacting protein; unrip
Mitogen-activated protein kinase activator with wd repeats; mawd
Mapk activator with wd repeats
CLONING
Hunt et al. (1999) stated that a number of viral and some cellular mRNAs are translated by an unusual mechanism involving internal ribosome entry sites (IRES). Some viruses require cellular factors (e.g., PTB; 600693) to stimulate the activity of viral IRES. By biochemical purification of rhinovirus IRES-stimulating activity from HeLa cells, micropeptide sequence analysis, EST database searching, and PCR analysis, Hunt et al. (1999) identified cDNAs encoding UNR (CSDE1; 191510) and STRAP, which they called UNRIP (UNR-interacting protein). Sequence analysis predicted that the 350-amino acid UNRIP protein, which is 25% identical to EIF3S2 (603911), contains 6 WD repeats. Coimmunoprecipitation analysis indicated that UNRIP interacts with UNR, which acts synergistically with PTB to stimulate translation dependent on the rhinovirus IRES. By searching EST databases for proteins resembling EIF3S2 and by RT-PCR of a placenta cDNA library, Matsuda et al. (2000) isolated cDNAs encoding STRAP, which they termed mitogen-activated protein kinase (MAPK) activator with WD repeats, or MAWD. Northern blot and RT-PCR analyses revealed ubiquitous expression of a 2.0-kb MAWD transcript. Western blot analysis showed that overexpression of MAWD induces expression of activated MAPK and correlates with anchorage-independent growth in vitro. PCR and immunoblot analyses detected expression of MAWD as a 39-kD protein in breast cancer but not normal tissue. Immunohistochemical analysis demonstrated cytoplasmic expression in tumor cells. Matsuda et al. (2000) proposed that the MAWD gene may be a frequent target for alteration in breast cancer.GENE FUNCTION
Spliceosomal uridine-rich small nuclear ribonucleoprotein (snRNP) assembly is an active process mediated by the macromolecular SMN complex (see SMN1, 600354). This complex contains the SMN1 protein and 6 additional proteins named GEMIN2 (SIP1; 602595) to GEMIN7 (607419), according to their localization to nuclear structures termed gems. Grimmler et al. (2005) showed that UNRIP is integrated into a complex with UNR or with the SMN complex in vivo in a mutually exclusive manner. In the latter case, UNRIP is recruited to the active SMN complex via a stable interaction with GEMIN7. However, unlike SMN and the gemins, UNRIP localized predominantly to the cytoplasm and was absent from gems/Cajal bodies. RNAi-induced reduction of UNRIP protein levels led to enhanced accumulation of SMN in the nucleus as evident by the increased formation of nuclear gems/Cajal bodies. Grimmler et al. (2005) concluded that UNRIP is the first component of the uridine-rich snRNP assembly machinery that associates with the SMN complex in a compartment-specific way, and it may play a crucial role in the intracellular distribution of the SMN complex.MAPPING
Matsuda et al. (2000) mapped the STRAP gene to chromosome 12q11-q12 by radiation hybrid analysis. However, Gross (2010) mapped the STRAP gene to chromosome 12p12.3 based on an alignment of the STRAP sequence (GenBank GENBANK BC000162) with the genomic sequence (GRCh37). ... 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 605986 was added.