Far upstream element-binding protein 2 (KHSRP)
The protein contains 711 amino acids for an estimated molecular weight of 73115 Da.
Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs. (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.
- 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.
- 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.
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Biological Process
3'-UTR-mediated mRNA destabilization
Cellular response to cytokine stimulus
Gene expression
MiRNA metabolic process
MRNA catabolic process
MRNA processing
MRNA transport
Negative regulation of low-density lipoprotein particle clearance
Negative regulation of nitric oxide biosynthetic process
Positive regulation of mRNA catabolic process
Positive regulation of transcription by RNA polymerase II
Regulation of gene expression
Regulation of miRNA metabolic process
Regulation of mRNA stability
Regulation of transcription, DNA-templated
RNA splicing
RNA splicing, via transesterification reactions
Transcription, DNA-templated
Molecular Function
DNA binding
MRNA 3'-UTR AU-rich region binding
MRNA binding
Poly(A) RNA binding
RNA binding
The reference OMIM entry for this protein is 603445
Kh-type splicing regulatory protein; khsrp
Ksrp
Far upstream element-binding protein 2; fubp2
Fuse-binding protein 2; fbp2
DESCRIPTION
The KHSRP gene encodes a multifunctional RNA-binding protein implicated in a variety of cellular processes, including transcription, alternative pre-mRNA splicing, and mRNA localization (Min et al., 1997; Gherzi et al., 2004).CLONING
The pre-mRNA of the protooncogene SRC (190090) contains an 18-nucleotide exon, N1, that is spliced into the mRNA in neuronal cells but is excluded in nonneuronal cells. N1 exon inclusion in neurons is under the positive control of an intronic regulatory sequence called the downstream control sequence (DCS). Using neuronal cell extracts, Min et al. (1995) isolated a complex that assembles specifically onto DCS RNA and that is required for N1 exon splicing in vitro. UV-crosslinking experiments identified HNRNPF (601037), a neuron-specific 75-kD protein (p75) doublet, and 4 non-cell-type-specific proteins as components of the DCS complex. By PCR of cDNA from a neuronal cell line using degenerate primers based on a partial p75 protein sequence, Min et al. (1997) isolated a partial p75 cDNA. They screened cDNA and genomic libraries and identified additional clones corresponding to the entire p75 coding region. The predicted 711-amino acid protein contains a proline/glycine-rich N terminus and a C-terminal domain that is rich in proline, glycine, alanine, and glutamine. The central region contains 4 tandemly repeated KH domains (see 602449), leading the authors to rename the protein 'KH-type splicing regulatory protein' (KSRP). Using Northern and Western blot analysis, Min et al. (1997) demonstrated that KSRP is expressed in both neuronal and nonneuronal cells, although it is approximately 3-fold more abundant in neuronal cells. They stated that the neuronal cell-specific crosslinking observed must arise from factors other than the relative levels of KSRP in various cell types. Davis-Smyth et al. (1996) identified KSRP (which they called FBP2) and FBP3 (FUBP3; 603536) as proteins related to the far upstream element-binding protein FBP1 (FUBP1; 603444). All 3 proteins had the same general architecture, with 3 distinct domains including a central nucleic acid-binding region containing KH motifs.GENE FUNCTION
Min et al. (1997) identified KSRP as part of a complex that assembles onto DCS RNA and is required for splicing of the N1 exon of SRC in vitro. Antibodies against KSRP inhibited both the assembly of the DCS complex and the in vitro splicing of the N1 exon. The KSRP antibodies did not bind to complexes already assembled onto the DCS. Instead, they blocked the complexes from assembling. Davis-Smyth et al. (1996) found that the FBPs, including FBP2, each bound specifically to 1 strand of the far upstream element (FUSE) originally identified upstream of MYC (190080), and each possessed a potent C-terminal activation domain. AU-rich elements (AREs) in the 3-prime UTR of inherently unstable mRNAs act as instability determinants by interacting with ARE-binding proteins that promote mRNA decay. Using human cell lines, Gherzi et al. (2004) demonstrated that KSRP is an essential factor for ARE-directed mRNA decay. Some of the KH motifs of KSRP directly mediated RNA binding, mRNA decay, and interactions with the exosome and poly(A) ribonuclease (PARN; 604212). The ability of KH domains to promote mRNA decay correlated with their ability to bind ARE and associate with RNA-degrading enzymes. Gherzi et al. (2004) concluded that the KH domains of KSRP promote rapid mRNA decay by ... 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
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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603445 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed