HNRNPK phospho S284

Function

One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841).

Involvement in disease

Au-Kline syndrome

AUKS

A disorder characterized by intellectual disability, facial dysmorphism, cardiac defects, and connective tissue and skeletal abnormalities. Dysmorphic features include long palpebral fissures, ptosis, a broad prominent nasal bridge, hypoplastic alae nasi, an open downturned mouth, ears with underdeveloped and thick helices, high palate, and a unique tongue with a prominent median crease. Hypotonia, hyporeflexia, and high pain tolerance are additional features.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Arg-296 and Arg-299 are dimethylated, probably to asymmetric dimethylarginine.

Sumoylated by CBX4. Sumoylation is increased upon DNA damage, such as that produced by doxorubicin, etoposide, UV light and camptothecin, due to enhanced CBX4 phosphorylation by HIPK2 under these conditions.

Ubiquitinated by MDM2. Doxorubicin treatment does not affect monoubiquitination, but slightly decreases HNRNPK poly-ubiquitination.

O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.

Cellular localization

• Cytoplasm
• Nucleus
• Nucleoplasm
• Cell projection
• Podosome
• Recruited to p53/TP53-responsive promoters, in the presence of functional p53/TP53 (PubMed:16360036). In case of ASFV infection, there is a shift in the localization which becomes predominantly nuclear (PubMed:18775702).

Alternative names

• HNRPK
• HNRNPK
• HNRPK
• Heterogeneous nuclear ribonucleoprotein K
• hnRNP K
• Transformation up-regulated nuclear protein
• TUNP

Database links

• swissprot:P61978

Target type

Proteins

Primary research area

Epigenetics

Molecular weight

50976Da