Heterogeneous nuclear ribonucleoproteins C1/C2

Function

Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles. 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. Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides. 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.

Classification

Family (Pfam)

PF00076 RRM_1

InterPro

hnRNP_C, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf, RRM_dom, RRM_HNRPC/RALY_subfam

Functional cluster

RRM RNA-Binding & Protein Kinases

Experimental structures · PDB · 5

• 1TXP NMR
• 1WF2 NMR
• 2MXY NMR
• 2MZ1 NMR
• 3LN4 X-ray 1.30A

A predicted model is available from AlphaFold.

Gene Ontology · 25

• GO:0015629 actin cytoskeleton
• GO:0071013 catalytic step 2 spliceosome
• GO:0000785 chromatin
• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0005576 extracellular region
• GO:0016020 membrane
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0032991 protein-containing complex
• GO:0005681 spliceosomal complex
• GO:0005697 telomerase holoenzyme complex
• GO:0042802 identical protein binding
• GO:0003730 mRNA 3'-UTR binding
• GO:1990247 N6-methyladenosine-containing RNA reader activity
• GO:0031492 nucleosomal DNA binding
• GO:0008266 poly(U) RNA binding
• GO:0003723 RNA binding
• GO:0070034 telomerase RNA binding
• GO:0070935 3'-UTR-mediated mRNA stabilization
• GO:0006338 chromatin remodeling
• GO:0000398 mRNA splicing, via spliceosome
• GO:0032211 negative regulation of telomere maintenance via telomerase
• GO:0001649 osteoblast differentiation
• GO:0008380 RNA splicing

Disease associations

• intellectual developmental disorder, autosomal dominant 74 MONDO:0958203

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Heterogeneous nuclear ribonucleoprotein C 1.00
• Heterogeneous nuclear ribonucleoprotein C 1.00
• Heterogeneous nuclear ribonucleoproteins C1/C2 0.99
• Heterogeneous nuclear ribonucleoprotein C 0.98
• Heterogeneous nuclear ribonucleoprotein C 0.92
• RNA-binding Raly-like protein 0.90
• RNA-binding Raly-like protein 0.90
• Heterogeneous nuclear ribonucleoprotein C-like 1 0.89
• RNA-binding Raly-like protein 0.89
• Heterogeneous nuclear ribonucleoprotein C-like 2 0.87
• Heterogeneous nuclear ribonucleoprotein C-like 4 0.85
• Heterogeneous nuclear ribonucleoprotein C-like 3 0.85

Co-cited proteins · studied together in the literature

• Heterogeneous nuclear ribonucleoproteins A2/B1 3 shared papers
• 14-3-3 protein epsilon 1 shared papers
• N(6)-adenosine-methyltransferase non-catalytic subunit METTL14 1 shared papers
• N(6)-adenosine-methyltransferase catalytic subunit METTL3 1 shared papers
• Actin, cytoplasmic 1 2 shared papers
• ATP-dependent RNA helicase A 2 shared papers
• Heterogeneous nuclear ribonucleoprotein M 1 shared papers
• Peptidyl-prolyl cis-trans isomerase A 1 shared papers
• TAR DNA-binding protein 43 1 shared papers
• RNA-binding motif protein, X chromosome 1 shared papers
• Adenylyl cyclase-associated protein 1 1 shared papers
• TAR DNA-binding protein 43 1 shared papers

Literature · 43 cited papers

• Nucleo-cytoplasmic shuttling of 14-3-3 epsilon carrying hnRNP C promotes autophagy. Cancer Biol. Ther. · 2023
• HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder. Am. J. Hum. Genet. · 2023
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• SUMO-2 orchestrates chromatin modifiers in response to DNA damage. Cell Rep. · 2015
• System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability. Mol. Cell. Proteomics · 2015
• N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature · 2015
• Peptidylprolyl isomerase A governs TARDBP function and assembly in heterogeneous nuclear ribonucleoprotein complexes. Brain · 2015
• Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
• Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. Proc. Natl. Acad. Sci. U.S.A. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• … and 31 more in the literature graph