Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC)
The protein contains 306 amino acids for an estimated molecular weight of 33670 Da.
Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles (PubMed:8264621). Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules (PubMed:12509468, PubMed:16010978, PubMed:7567451, PubMed:8264621). Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides (PubMed:8264621). May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing (PubMed:25719671). (updated: Jan. 31, 2018)
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.
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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| Variant | Description |
|---|---|
| dbSNP:rs3272 |
Biological Process
3'-UTR-mediated mRNA stabilization
ATP-dependent chromatin remodeling
Gene expression
MRNA splicing, via spliceosome
Negative regulation of telomere maintenance via telomerase
Osteoblast differentiation
RNA metabolic process
RNA splicing
Cellular Component
Actin cytoskeleton
Catalytic step 2 spliceosome
Chromatin
Cytosol
Extracellular exosome
Extracellular region
Membrane
Nuclear chromatin
Nucleoplasm
Nucleus
Pronucleus
Protein complex
Protein-containing complex
Spliceosomal complex
Telomerase holoenzyme complex
Molecular Function
Identical protein binding
MRNA 3'-UTR binding
N6-methyladenosine-containing RNA binding
Nucleosomal DNA binding
Nucleotide binding
Poly(A) RNA binding
Poly(U) RNA binding
RNA binding
RNA polymerase II cis-regulatory region sequence-specific DNA binding
RNA polymerase II distal enhancer sequence-specific DNA binding
Telomerase RNA binding
The reference OMIM entry for this protein is 164020
Heterogeneous nuclear ribonucleoprotein c; hnrnpc
Hnrpc nuclear ribonucleoprotein particle c1 protein, included
Nuclear ribonucleoprotein particle c2 protein, included
DESCRIPTION
The primary nuclear transcripts of RNA polymerase II, some of which are precursors to cytoplasmic mRNA (pre-mRNA), are collectively referred to as heterogeneous nuclear RNAs (hnRNAs). At least 20 of these proteins, designated A1 (34 kD) through U (120 kD), are present in abundance. In the nucleus they are found in association with a specific set of proteins to form ribonucleoprotein (hnRNP) particles. In vertebrates, the C proteins, C1 and C2, are major constituents of these particles. The 2 are antigenically closely related phosphoproteins, which bind tightly to RNA in vitro (Nakagawa et al., 1986).CLONING
Nakagawa et al. (1986) cloned cDNA for the hnRNA C proteins. Genomic blot analysis showed homologous DNA sequences across eukaryotes from human to yeast, indicating that the hnRNA C proteins are members of a conserved gene family. Burd et al. (1989) reported the complete primary structure of the hnRNP proteins A2, B1, and C2; A1, C1, and L had previously been sequenced. They suggested that the C1 and C2 proteins are produced by alternative splicing of a single gene transcript. Merrill et al. (1989) found that C1 and C2 differ by the presence of a 13-amino acid insert in C2, after either glycine-106 or serine-107 of C1. The additional 13 amino acids account for the molecular mass difference of C2 on SDS polyacrylamide gel electrophoresis. Otherwise C1 and C2 are identical; furthermore, the 3-prime and 5-prime untranslated portions of the 2 mRNAs are identical (Swanson et al., 1987).MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HNRNPC gene to chromosome 14 (TMAP RH70234).GENE FUNCTION
Locus control regions (LCRs) are regulatory DNA sequences located many kilobases away from their cognate promoters. Mahajan et al. (2005) found that an LCR-associated remodeling complex (LARC) purified from a human erythroleukemia cell line exists as a single homogeneous complex of hnRNP C1 and C2, the chromatin remodeling SWI/SNF complex (see 600014), and the nucleosome remodeling and deacetylating (NURD; see 603526)/MECP1 (156535) complex. Chen et al. (2006) purified the nuclear response element-binding protein (REBiP) identified by Chen et al. (2003) in a patient with vitamin D-dependent rickets type 2B (VDDR2B; 600785) and found a tryptic fragment bearing 100% sequence identity with the human hnRNP C1 and C2 proteins (164020). Tryptic peptide sequencing followed by Western blot analysis confirmed that cells from the VDDR2B patient overexpressed a pair of anti-hnRNP C1/C2-reactive proteins of 39-40 kD, compatible with the hnRNPC1 and the slightly larger hnRNPC2. When overexpressed in vitamin D-responsive cells, cDNAs for both C1 and C2 inhibited VDR (vitamin D receptor; 601769)-VDRE (vitamin D response element)-directed transactivation by 23% and 42%, respectively (p less than 0.005 for both). In contrast, transient expression of an hnRNP C1/C2 small interfering RNA (siRNA) increased VDR transactivation by 39% (p less than 0.005). Chromatin immunoprecipitation studies revealed the presence of REBiP in vitamin D-responsive human cells and indicated that the normal pattern of 1,25-dihydroxy vitamin D-initiated cyclical movement of the VDR on and off the VDRE is legislated by competitive, reciprocal occupancy of the VDRE by hnRNP C1/C2. The temporal and reciprocal pattern of VDR and hnRNP C1/C2 interaction with the VDRE was lost in VDDR2B cells overexpressing the hnRNP C ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 164020 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed