UniProt functional annotation for P78317



	UniProt functional annotation for P78317

UniProt code: P78317.

Organism: Homo sapiens (Human).

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

Function: E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys- 48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:19307308, ECO:0000269|PubMed:20026589, ECO:0000269|PubMed:20212317, ECO:0000269|PubMed:20943951}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;

Pathway: Protein modification; protein ubiquitination.

Subunit: Homodimer (via RING-type zinc finger domain). Interacts with GSC2 (By similarity). Interacts with AR/the androgen receptor and TBP (By similarity). Interacts with TCF20 (By similarity). Interacts with PATZ1. Interacts with TRPS1; negatively regulates TRPS1 transcriptional repressor activity. Interacts with PML; SUMO1-dependent. Interacts with PML; SUMO2-dependent. Interacts with PARP1. Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform PML-6). Interacts with PRDM1/Blimp-1 (PubMed:28842558). {ECO:0000250, ECO:0000269|PubMed:10713105, ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:15707587, ECO:0000269|PubMed:19779455, ECO:0000269|PubMed:20943951, ECO:0000269|PubMed:23028697, ECO:0000269|PubMed:28842558}.

Subcellular location: Cytoplasm. Nucleus. Nucleus, PML body. Nucleus, nucleoplasm.

Tissue specificity: Widely expressed at low levels in many tissues; highly expressed in testis. {ECO:0000269|PubMed:9479498}.

Domain: The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate. {ECO:0000269|PubMed:18408734}.

Domain: The RING-type zinc finger domain is required for the ubiquitination of polysumoylated substrates. {ECO:0000250|UniProtKB:O88846}.

Ptm: Sumoylated; conjugated by one or two SUMO1 moieties. {ECO:0000250}.

Ptm: Autoubiquitinated. {ECO:0000250}.

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:		E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys- 48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation. {ECO:0000269\|PubMed:12885770, ECO:0000269\|PubMed:18408734, ECO:0000269\|PubMed:19307308, ECO:0000269\|PubMed:20026589, ECO:0000269\|PubMed:20212317, ECO:0000269\|PubMed:20943951}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Homodimer (via RING-type zinc finger domain). Interacts with GSC2 (By similarity). Interacts with AR/the androgen receptor and TBP (By similarity). Interacts with TCF20 (By similarity). Interacts with PATZ1. Interacts with TRPS1; negatively regulates TRPS1 transcriptional repressor activity. Interacts with PML; SUMO1-dependent. Interacts with PML; SUMO2-dependent. Interacts with PARP1. Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform PML-6). Interacts with PRDM1/Blimp-1 (PubMed:28842558). {ECO:0000250, ECO:0000269\|PubMed:10713105, ECO:0000269\|PubMed:12885770, ECO:0000269\|PubMed:15707587, ECO:0000269\|PubMed:19779455, ECO:0000269\|PubMed:20943951, ECO:0000269\|PubMed:23028697, ECO:0000269\|PubMed:28842558}.
Subcellular location:		Cytoplasm. Nucleus. Nucleus, PML body. Nucleus, nucleoplasm.
Tissue specificity:		Widely expressed at low levels in many tissues; highly expressed in testis. {ECO:0000269\|PubMed:9479498}.
Domain:		The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate. {ECO:0000269\|PubMed:18408734}.
Domain:		The RING-type zinc finger domain is required for the ubiquitination of polysumoylated substrates. {ECO:0000250\|UniProtKB:O88846}.
Ptm:		Sumoylated; conjugated by one or two SUMO1 moieties. {ECO:0000250}.
Ptm:		Autoubiquitinated. {ECO:0000250}.