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Heterogeneous nuclear ribonucleoprotein C (C1/C2)
Protein HNRPC PDB 1wf2.png
PDB rendering based on 1wf2.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM164020 MGI107795 HomoloGene74524 GeneCards: HNRNPC Gene
Species Human Mouse
Entrez 3183 15381
Ensembl ENSG00000092199 ENSMUSG00000060373
UniProt P07910 Q9Z204
RefSeq (mRNA) NM_001077442 NM_001170981
RefSeq (protein) NP_001070910 NP_001164452
Location (UCSC) Chr 14:
21.21 – 21.27 Mb
Chr 14:
52.07 – 52.1 Mb
PubMed search [1] [2]

Heterogeneous nuclear ribonucleoproteins C1/C2 is a protein that in humans is encoded by the HNRNPC gene.[1][2]

It is abnormally expressed in fetuses of both IVF and ICSI, which may contribute to the increase risk of birth defects in these ART.[3]


This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing(reference: Koenig J. nature structural and Molecular Biology 2010: iCLIP) and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. Transcriptional regulation by hormonal 1,25-dihydroxyvitamin D(3) (calcitriol) involves occupancy of vitamin D response elements (VDREs) by HNRNPC or 1,25(OH)(2)D(3)-bound vitamin D receptor (VDR).[4][5][6] This relationship is disrupted by elevated HNRNPC, causing a form of hereditary vitamin D-resistant rickets (HVDRR) in both humans[4] and non-human primates.[7] The protein encoded by this gene can act as a tetramer and is involved in the assembly of 40S hnRNP particles. Species-specific tetramerization of HNRNPC subunits is important to its nucleic acid binding, whereby over-expression of major human HNRNPC subunits in mouse osteoblastic cells confers vitamin D resistance.[8] Multiple transcript variants encoding at least two different isoforms have been described for this gene.[2]


HNRNPC has been shown to interact with Grb2.[9]


  1. ^ Nakagawa TY, Swanson MS, Wold BJ, Dreyfuss G (May 1986). "Molecular cloning of cDNA for the nuclear ribonucleoprotein particle C proteins: a conserved gene family". Proc Natl Acad Sci U S A 83 (7): 2007–11. doi:10.1073/pnas.83.7.2007. PMC 323219. PMID 3457372. 
  2. ^ a b "Entrez Gene: HNRPC heterogeneous nuclear ribonucleoprotein C (C1/C2)". 
  3. ^ Zhang Y, Zhang YL, Feng C, Wu YT, Liu AX, Sheng JZ, Cai J, Huang HF (September 2008). "Comparative proteomic analysis of human placenta derived from assisted reproductive technology". Proteomics 8 (20): 4344–56. doi:10.1002/pmic.200800294. PMID 18792929. 
  4. ^ a b Lisse TS, Liu T, Irmler M, Beckers J, Chen H, Adams JS, Hewison M (March 2011). "Gene targeting by the vitamin D response element binding protein reveals a role for vitamin D in osteoblast mTOR signaling.". FASEB J 25 (3): 937–47. doi:10.1096/fj.10-172577. PMID 21123297. 
  5. ^ Chen H, Hewison M, Adams JS (December 2006). "Functional characterization of heterogeneous nuclear ribonuclear protein C1/C2 in vitamin D resistance: a novel response element-binding protein.". J Biol Chem 281 (51): 39114–20. doi:10.1074/jbc.m608006200. PMID 17071612. 
  6. ^ Lisse TS, Hewison M, Adams JS (March 2011). "Hormone response element binding proteins: novel regulators of vitamin D and estrogen signaling.". Steroids 76 (4): 331–9. doi:10.1016/j.steroids.2011.01.002. PMID 21236284. 
  7. ^ Adams JS, Chen H, Chun RF, Nguyen L, Wu S, Ren SY, Barsony J, Gacad MA (Feb 2003). "Novel regulators of vitamin D action and metabolism: Lessons learned at the Los Angeles zoo.". J Cell Biochem 88 (2): 308–14. doi:10.1002/jcb.10333. PMID 12520531. 
  8. ^ Lisse TS, Vadivel K, Bajaj SP, Chun RF, Hewison M, Adams JS (July 2014). "The heterodimeric structure of heterogeneous nuclear ribonucleoprotein C1/C2 dictates 1,25-dihydroxyvitamin D-directed transcriptional events in osteoblasts.". Bone Research 2. doi:10.1038/boneres.2014.11. PMID 25506471. 
  9. ^ Romero F, Ramos-Morales F, Domínguez A, Rios RM, Schweighoffer F, Tocqué B, Pintor-Toro JA, Fischer S, Tortolero M (Mar 1998). "Grb2 and its apoptotic isoform Grb3-3 associate with heterogeneous nuclear ribonucleoprotein C, and these interactions are modulated by poly(U) RNA". J. Biol. Chem. 273 (13): 7776–81. doi:10.1074/jbc.273.13.7776. PMID 9516488. 

Further reading[edit]