Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD)
The protein contains 355 amino acids for an estimated molecular weight of 38434 Da.
Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Also binds to double- and single-stranded DNA sequences in a specific manner and functions a transcription factor. Each of the RNA-binding domains specifically can bind solely to a single-stranded non-monotonous 5'-UUAG-3' sequence and also weaker to the single-stranded 5'-TTAGGG-3' telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. Binding of RRM1 to DNA inhibits the formation of DNA quadruplex structure which may play a role in telomere elongation. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. May play a role in the regulation of the rhythmic expression of circadian clock core genes. Directly binds to the 3'UTR of CRY1 mRNA and induces CRY1 rhythmic translation. May also be involved in the regulation of PER2 translation. (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.
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Biological Process
3'-UTR-mediated mRNA destabilization
Cellular response to amino acid stimulus
Cellular response to estradiol stimulus
Cellular response to nitric oxide
Cellular response to putrescine
Cerebellum development
Circadian regulation of translation
Gene expression
Hepatocyte dedifferentiation
Liver development
MRNA splicing, via spliceosome
MRNA stabilization
MRNA transcription by RNA polymerase II
Positive regulation of gene expression
Positive regulation of telomerase RNA reverse transcriptase activity
Positive regulation of telomere capping
Positive regulation of transcription by RNA polymerase II
Positive regulation of transcription, DNA-templated
Positive regulation of translation
Regulation of circadian rhythm
Regulation of gene expression
Regulation of mRNA stability
Regulation of RNA metabolic process
Regulation of telomere maintenance
Regulation of transcription, DNA-templated
Response to calcium ion
Response to drug
Response to electrical stimulus
Response to rapamycin
Response to sodium phosphate
RNA catabolic process
RNA metabolic process
RNA processing
RNA splicing
Transcription, DNA-templated
Cellular Component
Cytosol
Extracellular exosome
Intracellular ribonucleoprotein complex
Nuclear chromatin
Nucleoplasm
Nucleus
Ribonucleoprotein complex
Synapse
Molecular Function
Chromatin binding
Histone deacetylase binding
Minor groove of adenine-thymine-rich DNA binding
MRNA 3'-UTR AU-rich region binding
MRNA binding
Nucleotide binding
Poly(A) RNA binding
RNA binding
Sequence-specific DNA binding
Sequence-specific double-stranded DNA binding
Telomeric DNA binding
Transcription factor binding
The reference OMIM entry for this protein is 601324
Heterogeneous nuclear ribonucleoprotein d; hnrnpd
Hnrpd
Au-rich element rna-binding protein 1, 37-kd; auf1
Are-binding protein auf1, type a; auf1a
CLONING
The cytoplasmic instability of certain mRNAs is a critical regulatory component of gene expression. The mRNAs encoded by many genes important for controlling cell growth are very unstable, having half-lives on the order of 15 to 40 minutes. Mutations that stabilize certain mRNAs, such as FOS (164810) and MYC (190080), can contribute to oncogenic transformation. One class of cis-acting instability determinants is composed of AU-rich elements (AREs) found within the 3-prime untranslated regions of many protooncogenes and cytokine mRNAs (summarized by Wagner et al., 1996). Brewer (1991) and Zhang et al. (1993) described the purification and characterization of AUF1, a potential mediator of ARE-directed mRNA degradation. AUF1 binds with high affinity to RNA molecules that contain ARE sequences from MYC, FOS, and GMCSF (138960) mRNAs. By contrast, AUF1 does not bind with high affinity to RNA sequences that lack an ARE. AUF1 is composed of at least 2 immunologically cross-reactive polypeptides with apparent molecular masses of 37 and 40 kD. Zhang et al. (1993) used purified AUF1 protein to make polyclonal anti-AUF1 antibodies. They screened a HeLa cell expression library and isolated a clone (designated p37AUF1) that bound to AREs when tested. The 2.5-kb cDNA contains an ORF of 861 bp and produced a 37-kD in vitro translation product that comigrated with the p37AUF1 polypeptide. Sequence analysis revealed 2 nonidentical RNA recognition motifs (RRMs), a glutamine-rich region, and 3 putative phosphorylation sites. Metabolic labeling experiments showed that the translated protein is phosphorylated in K562 cells. Biochemical fractionation and immunofluorescence data suggested to Zhang et al. (1993) that AUF1 protein localizes to both the nucleus and the cytoplasm. Based on its homology to other RRM-containing proteins in GenBank, Zhang et al. (1993) speculated that p37AUF1 is part of a family of related proteins distinct from the hnRNP proteins, which includes the DL4 protein, the human homolog of lambda C6, and the human hnRNP A/B-like protein (see 600124). Wagner et al. (1996) noted that the RRMs of p37AUF1 are highly homologous with those of murine AUF1 (98% identity) and those of the Drosophila melanogaster 'Squid' gene product (43% identity), suggesting conserved functions. Wagner et al. (1996) cloned cDNAs encoding the AUF1 family of ARE-binding proteins from human and murine cDNA libraries. Wagner et al. (1998) identified 4 AUF1 isoforms of 37 kD (p37AUF), 40 kD (p40AUF), 42 kD (p42AUF), and 45 kD (p45AUF), which result from alternative pre-mRNA splicing. The isoforms differ by the presence or absence of a 19- and/or a 49-amino acid insert.GENE FUNCTION
Wagner et al. (1998) showed that the 4 AUF1 isoforms exhibit an approximately 35-fold range in ARE-binding affinities, with p37AUF having the highest affinity and p40AUF having the lowest affinity. Cytokine and protooncogene mRNAs are rapidly degraded through AU-rich elements in the 3-prime untranslated region. Rapid decay involves AU-rich binding protein AUF1, which complexes with heat-shock proteins HSC70 (600816) and HSP70 (see 140550), translation initiation factor EIF4G (600495), and poly(A)-binding protein (PABP; 604679). AU-rich mRNA decay is associated with displacement of EIF4G from AUF1, ubiquitination of AUF1, and degradation of AUF1 by proteasomes. Induction of HSP70 by heat shock, downregulation of the ubiquitin-proteasome network, or inactivation ... 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601324 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed