UniProt functional annotation for P23497



	UniProt functional annotation for P23497

UniProt code: P23497.

Organism: Homo sapiens (Human).

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

Function: Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation. {ECO:0000269|PubMed:11909962, ECO:0000269|PubMed:14647468, ECO:0000269|PubMed:15247905, ECO:0000269|PubMed:15592518, ECO:0000269|PubMed:15767676, ECO:0000269|PubMed:16177824, ECO:0000269|PubMed:17245429, ECO:0000269|PubMed:21274506, ECO:0000269|PubMed:21880768}.

Subunit: Homodimer; isoforms are able to heterodimerize. Interacts with members of the HP1 family of nonhistone chromosomal protein, such as CBX5 and CBX3 via the PxVxL motif. Interacts with ETS1; the interaction is direct and modulates ETS1 transcriptional activity. Interacts with the MRN complex which is composed of two heterodimers RAD50/MRE11 associated with a single NBN; recruits the complex to PML-related bodies. Interacts with HIPK2; positively regulates TP53-dependent transcription. Interacts with CASP8AP2; may negatively regulate CASP8AP2 export from the nucleus to the cytoplasm. Interacts with SUMO1P1/SUMO5 (PubMed:27211601). {ECO:0000269|PubMed:11313457, ECO:0000269|PubMed:11909962, ECO:0000269|PubMed:12470659, ECO:0000269|PubMed:14647468, ECO:0000269|PubMed:15247905, ECO:0000269|PubMed:15767676, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:17245429, ECO:0000269|PubMed:27211601}.

Subunit: (Microbial infection) Interacts with Epstein-Barr virus EBNA- LP; this interaction is important for EBNA-LP coactivator activity. {ECO:0000269|PubMed:16177824}.

Subunit: (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL123; may play a role in infection by the virus. {ECO:0000269|PubMed:21880768}.

Subcellular location: Nucleus. Nucleus, PML body {ECO:0000269|PubMed:27211601}. Cytoplasm. Note=Differences in the subnuclear localization of the different isoforms seem to exist and may also be cell cycle- and interferon-dependent. Accumulates in the cytoplasm upon FAS activation.

Subcellular location: [Isoform Sp100-C]: Nucleus {ECO:0000269|PubMed:11313457}. Note=Forms a reticulate or track-like nuclear pattern with denser concentrations at the nuclear lamina and surrounding the nucleoli, a pattern reminiscent of heterochromatin-rich regions according to PubMed:11313457.

Tissue specificity: Widely expressed. Sp100-B is expressed only in spleen, tonsil, thymus, mature B-cell line and some T-cell line, but not in brain, liver, muscle or non-lymphoid cell lines.

Induction: Up-regulated by interferon, retinoic acid, TNF-alpha/TNFA and lipopolysaccharide (at protein level). Up-regulated following heat- shock. {ECO:0000269|PubMed:15247905, ECO:0000269|PubMed:15592518, ECO:0000269|PubMed:21880768}.

Domain: The HSR domain is important for the nuclear body targeting as well as for the dimerization. {ECO:0000269|PubMed:22086178}.

Domain: Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain. {ECO:0000269|PubMed:22086178}.

Ptm: Sumoylated. Sumoylation depends on a functional nuclear localization signal but is not necessary for nuclear import or nuclear body targeting.

Ptm: Sumoylated. Sumoylated with SUMO1. Sumoylation depends on a functional nuclear localization signal but is not necessary for nuclear import or nuclear body targeting. Sumoylation may stabilize the interaction with CBX5.

Ptm: (Microbial infection) Immediate early protein IE1 of human cytomegalovirus (HHV-5) interferes with the sumoylation of SP100. {ECO:0000269|PubMed:10233977}.

Miscellaneous: The major isoform Sp100-A, has a calculated molecular weight of 54 kDa, but exhibits aberrant electrophoretic mobilities, with an apparent molecular weight of 100 kDa.

Miscellaneous: [Isoform Sp100-A]: Major isoform. {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:		Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation. {ECO:0000269\|PubMed:11909962, ECO:0000269\|PubMed:14647468, ECO:0000269\|PubMed:15247905, ECO:0000269\|PubMed:15592518, ECO:0000269\|PubMed:15767676, ECO:0000269\|PubMed:16177824, ECO:0000269\|PubMed:17245429, ECO:0000269\|PubMed:21274506, ECO:0000269\|PubMed:21880768}.


Subunit:		Homodimer; isoforms are able to heterodimerize. Interacts with members of the HP1 family of nonhistone chromosomal protein, such as CBX5 and CBX3 via the PxVxL motif. Interacts with ETS1; the interaction is direct and modulates ETS1 transcriptional activity. Interacts with the MRN complex which is composed of two heterodimers RAD50/MRE11 associated with a single NBN; recruits the complex to PML-related bodies. Interacts with HIPK2; positively regulates TP53-dependent transcription. Interacts with CASP8AP2; may negatively regulate CASP8AP2 export from the nucleus to the cytoplasm. Interacts with SUMO1P1/SUMO5 (PubMed:27211601). {ECO:0000269\|PubMed:11313457, ECO:0000269\|PubMed:11909962, ECO:0000269\|PubMed:12470659, ECO:0000269\|PubMed:14647468, ECO:0000269\|PubMed:15247905, ECO:0000269\|PubMed:15767676, ECO:0000269\|PubMed:15882967, ECO:0000269\|PubMed:17245429, ECO:0000269\|PubMed:27211601}.
Subunit:		(Microbial infection) Interacts with Epstein-Barr virus EBNA- LP; this interaction is important for EBNA-LP coactivator activity. {ECO:0000269\|PubMed:16177824}.
Subunit:		(Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL123; may play a role in infection by the virus. {ECO:0000269\|PubMed:21880768}.
Subcellular location:		Nucleus. Nucleus, PML body {ECO:0000269\|PubMed:27211601}. Cytoplasm. Note=Differences in the subnuclear localization of the different isoforms seem to exist and may also be cell cycle- and interferon-dependent. Accumulates in the cytoplasm upon FAS activation.
Subcellular location:		[Isoform Sp100-C]: Nucleus {ECO:0000269\|PubMed:11313457}. Note=Forms a reticulate or track-like nuclear pattern with denser concentrations at the nuclear lamina and surrounding the nucleoli, a pattern reminiscent of heterochromatin-rich regions according to PubMed:11313457.
Tissue specificity:		Widely expressed. Sp100-B is expressed only in spleen, tonsil, thymus, mature B-cell line and some T-cell line, but not in brain, liver, muscle or non-lymphoid cell lines.
Induction:		Up-regulated by interferon, retinoic acid, TNF-alpha/TNFA and lipopolysaccharide (at protein level). Up-regulated following heat- shock. {ECO:0000269\|PubMed:15247905, ECO:0000269\|PubMed:15592518, ECO:0000269\|PubMed:21880768}.
Domain:		The HSR domain is important for the nuclear body targeting as well as for the dimerization. {ECO:0000269\|PubMed:22086178}.
Domain:		Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain. {ECO:0000269\|PubMed:22086178}.
Ptm:		Sumoylated. Sumoylation depends on a functional nuclear localization signal but is not necessary for nuclear import or nuclear body targeting.
Ptm:		Sumoylated. Sumoylated with SUMO1. Sumoylation depends on a functional nuclear localization signal but is not necessary for nuclear import or nuclear body targeting. Sumoylation may stabilize the interaction with CBX5.
Ptm:		(Microbial infection) Immediate early protein IE1 of human cytomegalovirus (HHV-5) interferes with the sumoylation of SP100. {ECO:0000269\|PubMed:10233977}.
Miscellaneous:		The major isoform Sp100-A, has a calculated molecular weight of 54 kDa, but exhibits aberrant electrophoretic mobilities, with an apparent molecular weight of 100 kDa.
Miscellaneous:		[Isoform Sp100-A]: Major isoform. {ECO:0000305}.