UniProt functional annotation for P61978



	UniProt functional annotation for P61978

UniProt code: P61978.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850}.

Subunit: Interacts with RBM42 and ZIK1 (By similarity). Interacts with BRDT (By similarity). Identified in the spliceosome C complex (PubMed:11991638). Interacts with ANKRD28 (PubMed:16564677). Interacts with ASFV p30 protein (PubMed:18775702). Interacts with DDX1 (PubMed:12183465). Interacts with MDM2; this interaction leads to ubiquitination and proteasomal degradation (PubMed:16360036). Interacts with p53/TP53 (PubMed:16360036). Interacts with IVNS1ABP (PubMed:23825951). Interacts with PPIA/CYPA (PubMed:25678563). {ECO:0000250|UniProtKB:P61979, ECO:0000250|UniProtKB:P61980, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12093748, ECO:0000269|PubMed:12183465, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:16564677, ECO:0000269|PubMed:18775702, ECO:0000269|PubMed:23825951, ECO:0000269|PubMed:25678563}.

Subunit: (Microbial infection) Interacts with HCV core protein (PubMed:9651361). {ECO:0000269|PubMed:9651361}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:1729596}. Nucleus, nucleoplasm {ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:1729596, ECO:0000269|PubMed:18775702, ECO:0000269|PubMed:22721921}. Cell projection, podosome {ECO:0000269|PubMed:22721921}. Note=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).

Induction: By DNA damage, including ionizing radiations and phleomycin treatment or UV irradiation. This induction requires ATM kinase activity (ionizing radiations and phleomycin) or ATR activity (UV irradiation). Up-regulation is due to protein stabilization. Constitutive protein levels are controlled by MDM2-mediated ubiquitination and degradation via the proteasome pathway. {ECO:0000269|PubMed:16360036}.

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

Ptm: 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. {ECO:0000269|PubMed:16564677, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:8107114}.

Ptm: Ubiquitinated by MDM2. Doxorubicin treatment does not affect monoubiquitination, but slightly decreases HNRNPK poly-ubiquitination. {ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:22825850}.

Ptm: O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. {ECO:0000269|PubMed:22967762}.

Mass spectrometry: [Isoform 1]: Mass=50976.25; Method=MALDI; Evidence={ECO:0000269|PubMed:11840567};

Disease: Au-Kline syndrome (AUKS) [MIM:616580]: 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. {ECO:0000269|PubMed:26173930}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=BAD92799.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000250, ECO:0000269\|PubMed:16360036, ECO:0000269\|PubMed:20673990, ECO:0000269\|PubMed:22825850}.


Subunit:		Interacts with RBM42 and ZIK1 (By similarity). Interacts with BRDT (By similarity). Identified in the spliceosome C complex (PubMed:11991638). Interacts with ANKRD28 (PubMed:16564677). Interacts with ASFV p30 protein (PubMed:18775702). Interacts with DDX1 (PubMed:12183465). Interacts with MDM2; this interaction leads to ubiquitination and proteasomal degradation (PubMed:16360036). Interacts with p53/TP53 (PubMed:16360036). Interacts with IVNS1ABP (PubMed:23825951). Interacts with PPIA/CYPA (PubMed:25678563). {ECO:0000250\|UniProtKB:P61979, ECO:0000250\|UniProtKB:P61980, ECO:0000269\|PubMed:11991638, ECO:0000269\|PubMed:12093748, ECO:0000269\|PubMed:12183465, ECO:0000269\|PubMed:16360036, ECO:0000269\|PubMed:16564677, ECO:0000269\|PubMed:18775702, ECO:0000269\|PubMed:23825951, ECO:0000269\|PubMed:25678563}.
Subunit:		(Microbial infection) Interacts with HCV core protein (PubMed:9651361). {ECO:0000269\|PubMed:9651361}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:1729596}. Nucleus, nucleoplasm {ECO:0000269\|PubMed:16360036, ECO:0000269\|PubMed:1729596, ECO:0000269\|PubMed:18775702, ECO:0000269\|PubMed:22721921}. Cell projection, podosome {ECO:0000269\|PubMed:22721921}. Note=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).
Induction:		By DNA damage, including ionizing radiations and phleomycin treatment or UV irradiation. This induction requires ATM kinase activity (ionizing radiations and phleomycin) or ATR activity (UV irradiation). Up-regulation is due to protein stabilization. Constitutive protein levels are controlled by MDM2-mediated ubiquitination and degradation via the proteasome pathway. {ECO:0000269\|PubMed:16360036}.
Ptm:		Arg-296 and Arg-299 are dimethylated, probably to asymmetric dimethylarginine.
Ptm:		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. {ECO:0000269\|PubMed:16564677, ECO:0000269\|PubMed:22825850, ECO:0000269\|PubMed:8107114}.
Ptm:		Ubiquitinated by MDM2. Doxorubicin treatment does not affect monoubiquitination, but slightly decreases HNRNPK poly-ubiquitination. {ECO:0000269\|PubMed:16360036, ECO:0000269\|PubMed:22825850}.
Ptm:		O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. {ECO:0000269\|PubMed:22967762}.
Mass spectrometry:		[Isoform 1]: Mass=50976.25; Method=MALDI; Evidence={ECO:0000269\|PubMed:11840567};
Disease:		Au-Kline syndrome (AUKS) [MIM:616580]: 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. {ECO:0000269\|PubMed:26173930}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=BAD92799.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};