RNA-binding motif protein, X chromosome (RBMX)

The protein contains 391 amino acids for an estimated molecular weight of 42332 Da.

 

RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of several pre-mRNAs. Binds to and stimulates transcription from the tumor suppressor TXNIP gene promoter; may thus be involved in tumor suppression. When associated with SAFB, binds to and stimulates transcription from the SREBF1 promoter. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Can either activate or suppress exon inclusion; acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN2. Represses the splicing of MAPT/Tau exon 10. Binds preferentially to single-stranded 5'-CC[A/C]-rich RNA sequence motifs localized in a single-stranded conformation; probably binds RNA as a homodimer. Binds non-specifically to pre-mRNAs. Plays also a role in the cytoplasmic TNFR1 trafficking pathways; promotes both the IL-1-beta-mediated inducible proteolytic cleavage of TNFR1 ectodomains and the release of TNFR1 exosome-like vesicles to the extracellular compartment. (updated: April 1, 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. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. 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.

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: 30%
Model score: 28

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The reference OMIM entry for this protein is 300199

Rna-binding motif protein, x chromosome; rbmx
Heterogeneous nuclear ribonucleoprotein g; hnrnpg rna-binding motif protein, x chromosome, retrogene, included; rbmxrt, included
Rna-binding motif protein, x chromosome, pseudogene 1, included; rbmxp1

CLONING

Le Coniat et al. (1992) cloned a cDNA encoding a nuclear 43-kD glycoprotein, identified as the G hnRNP protein. They designated the gene HNRPG. The HNRPG cDNA has 60% homology with RBMY1A1. Mazeyrat et al. (1999) isolated and sequenced 2 Rbmx mouse cDNA clones, which they named Rbmx1 and Rbmx2, with distinct 3-prime ends. RT-PCR showed that both Rbmx transcripts are ubiquitously expressed. Mazeyrat et al. (1999) concluded that, based on the absence of intronic sequence, the mouse Hnrpg gene is a retroposon derived from Rbmx.

GENE FUNCTION

The genes on the human Y chromosome fall into 2 classes with distinct evolutionary origins. Widely expressed, single-copy genes with X homologs that escape inactivation (X-Y shared genes) derive from the ancient proto X-Y chromosome pair. Testis-specific, multicopy genes with no X homologs originate from autosomes and have accumulated on a 'selfish Y' because of their male-specific function. Copies of genes in the RBMY gene family (see RBMY1A1, 400006) are candidate spermatogenesis genes because they are found in all 3 azoospermia factor (AZF) deletion intervals on the human Yq, which are associated with oligospermia or azoospermia (Vogt et al., 1997). An active X-borne homolog of the Y-borne RBMY gene was demonstrated in humans and marsupials by Delbridge et al. (1999) and in the mouse by Mazeyrat et al. (1999). Delbridge et al. (1999) stated that, like other gene pairs on the X and Y chromosomes (e.g., DFFRX/DFFRY; see 400005), RBMX retained a widespread function and RBMY evolved a male-specific function in spermatogenesis. Thus, RBMY1A1, far from belonging to a 'second class' of testis-specific elements, is a diverged X-Y shared gene. Venables et al. (2000) used a yeast 2-hybrid system to show that the RBMY gene product hnRNPG and a novel testis-specific relative (termed hnRNPG-T) interact with Tra2-beta (TRA2B; 602719), an activator of pre-mRNA splicing that is ubiquitous but highly expressed in testis. The RBMY gene product and Tra2-beta colocalized in 2 major domains in human spermatocyte nuclei. Incubation with the protein interaction domain of the RBMY gene product inhibited splicing in vitro of a specific pre-mRNA substrate containing an essential enhancer bound by Tra2-beta. The RNA-binding domain of RBM affected 5-prime splice site selection. The authors concluded that the hnRNPG family of proteins is involved in pre-mRNA splicing and hypothesized that RBM may be involved in Tra2-beta-dependent splicing in spermatocytes. Using in vivo splicing assays, Hofmann and Wirth (2002) identified hnRNPG and its paralog RBM as splicing factors that promoted the inclusion of SMN2 (601627) exon 7. Both hnRNPG and RBM nonspecifically bound RNA, but directly and specifically bound Htra2-beta1, an SR-like splicing factor which stimulates inclusion of exon 7 through a direct interaction with SMN2 exon 7 pre-mRNA. Using deletion mutants of hnRNPG, the authors demonstrated a specific protein-protein interaction of hnRNPG with Htra2-beta1, which mediated the inclusion of SMN2 exon 7 rather than the nonspecific interaction of hnRNPG with SMN pre-mRNA. These trans-acting splicing factors were also effective on endogenous SMN2 transcripts and increased the endogenous SMN protein level. The authors presented a model of how exon 7 mRNA processing may be regulated by these splicing factors. Nasim et al. (2003) showed that HNRNPG and the splicing activator protein TRA2B have opposite effe ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for RBMX

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300199 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed