Q63945 · SET_RAT
- ProteinProtein SET
- GeneSet
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids289 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher (By similarity).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | chromatin | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | perinuclear region of cytoplasm | |
Molecular Function | chromatin binding | |
Molecular Function | DNA binding | |
Molecular Function | histone binding | |
Biological Process | endothelial cell differentiation | |
Biological Process | nucleosome assembly | |
Biological Process | positive regulation of transcription by RNA polymerase II |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein SET
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ63945
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: In the cytoplasm, found both in the cytosol and associated with the endoplasmic reticulum. The SET complex is associated with the endoplasmic reticulum. Following CTL attack and cleavage by GZMA, moves rapidly to the nucleus, where it is found in the nucleoplasm, avoiding the nucleolus. Similar translocation to the nucleus is also observed for lymphocyte-activated killer cells after the addition of calcium (By similarity).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N,N,N-trimethylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000185664 | 2-289 | Protein SET | |||
Sequence: APKRQSAILPQPKKPRPVAAPKLEDKSASPGLPKGEKEQQEAIEHIDEVQNEIDRLNEQASEEILKVEQKYNKLRQPFFQKRSELIAKIPNFWVTTFVNHPQVSALLGEEDEEALHYLTRVEVTEFEDIKSGYRIDFYFDENPYFENKVLSKEFHLNESGDPSSKSTEIKWKSGKDLTKRSSQTQNKASRKRQHEEPESFFTWFTDHSDAGADELGEVIKDDIWPNPLQYYLVPDMDDEEGEAEDDDDDDEEEEGLEDIDEEGDEDEGEEDDDEDEGEEGEEDEGEDD | ||||||
Modified residue | 7 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 11 | In isoform Q63945-2; N6-acetyllysine | ||||
Sequence: P | ||||||
Modified residue | 15 | In isoform Q63945-2; Phosphoserine | ||||
Sequence: K | ||||||
Modified residue | 23 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 24 | In isoform Q63945-2; Phosphoserine | ||||
Sequence: L | ||||||
Modified residue | 28 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 62 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 67 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 145 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 149 | N6-acetyllysine | ||||
Sequence: K | ||||||
Cross-link | 153 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 171 | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
Isoform 2 is phosphorylated on Ser-15 and Ser-24.
Isoform 2 is acetylated on Lys-11.
Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group (By similarity).
N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated (By similarity).
Isoform 2
Cleaved after Lys-176 by GZMA. The cleavage inhibits its nucleosome assembly activity and disrupts the inhibition on NME1 (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed, with higher expression in brain, thymus, spleen and bone marrow, and lower expression in heart, liver and muscle.
Developmental stage
Higher expression in neonatal kidney than in adult. In the neonatal kidney, expressed more strongly in primitive nephrons undergoing early morphogenesis than in more developed structures. In 1-day old rat kidney, restricted to the first recognizable primitive nephron structures. Up-regulated after partial hepatectomy, with a peak after 24 hours.
Gene expression databases
Interaction
Subunit
Headphone-shaped homodimer. Isoform 1 and isoform 2 interact directly with each other and with ANP32A within the tripartite INHAT (inhibitor of acetyltransferases) complex. Isoform 1 and isoform 2 interact also with histones. Isoform 2 is a omponent of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1, but not NME2 or TREX2. Within this complex, directly interacts with ANP32A, NME1, HMGB2 and TREX1; the interaction with ANP32A is enhanced after cleavage. Interacts with APBB1, CHTOP, SETBP1, SGO1 (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-42 | Disordered | ||||
Sequence: MAPKRQSAILPQPKKPRPVAAPKLEDKSASPGLPKGEKEQQE | ||||||
Region | 31-77 | Dimerization | ||||
Sequence: PGLPKGEKEQQEAIEHIDEVQNEIDRLNEQASEEILKVEQKYNKLRQ | ||||||
Region | 78-224 | Earmuff domain | ||||
Sequence: PFFQKRSELIAKIPNFWVTTFVNHPQVSALLGEEDEEALHYLTRVEVTEFEDIKSGYRIDFYFDENPYFENKVLSKEFHLNESGDPSSKSTEIKWKSGKDLTKRSSQTQNKASRKRQHEEPESFFTWFTDHSDAGADELGEVIKDDI | ||||||
Region | 157-206 | Disordered | ||||
Sequence: LNESGDPSSKSTEIKWKSGKDLTKRSSQTQNKASRKRQHEEPESFFTWFT | ||||||
Compositional bias | 189-203 | Basic and acidic residues | ||||
Sequence: ASRKRQHEEPESFFT | ||||||
Region | 235-289 | Disordered | ||||
Sequence: PDMDDEEGEAEDDDDDDEEEEGLEDIDEEGDEDEGEEDDDEDEGEEGEEDEGEDD | ||||||
Compositional bias | 236-289 | Acidic residues | ||||
Sequence: DMDDEEGEAEDDDDDDEEEEGLEDIDEEGDEDEGEEDDDEDEGEEGEEDEGEDD |
Domain
A long alpha helix in the N-terminus mediates dimerization, while the earmuff domain is responsible for core histone and dsDNA binding. The C-terminal acidic domain mediates the inhibition of histone acetyltransferases and is required for the DNA replication stimulatory activity (By similarity).
Sequence similarities
Belongs to the nucleosome assembly protein (NAP) family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q63945-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsTAF-I alpha
- Length289
- Mass (Da)33,406
- Last updated1999-01-01 v2
- ChecksumE6EDD9DC4F1074E3
Q63945-2
- Name2
- SynonymsTAF-I beta
- Differences from canonical
- 1-36: MAPKRQSAILPQPKKPRPVAAPKLEDKSASPGLPKG → MSAPTAKASKKELNSNHDGADETS
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2JZ66 | A0A0G2JZ66_RAT | Pkn3 | 879 | ||
D3ZC07 | D3ZC07_RAT | Pkn3 | 958 | ||
A0A8I6AFH6 | A0A8I6AFH6_RAT | Pkn3 | 266 | ||
A0A8L2R247 | A0A8L2R247_RAT | Pkn3 | 328 | ||
A0A8I5ZLW3 | A0A8I5ZLW3_RAT | Set | 267 | ||
A0A8I5ZRC3 | A0A8I5ZRC3_RAT | Pkn3 | 815 | ||
A0A8I6G2K3 | A0A8I6G2K3_RAT | Setsip | 289 |
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_050443 | 1-36 | in isoform 2 | |||
Sequence: MAPKRQSAILPQPKKPRPVAAPKLEDKSASPGLPKG → MSAPTAKASKKELNSNHDGADETS | ||||||
Sequence conflict | 88 | in Ref. 2; AAP92538 | ||||
Sequence: A → T | ||||||
Sequence conflict | 181 | in Ref. 2; AAP92538 | ||||
Sequence: R → C | ||||||
Compositional bias | 189-203 | Basic and acidic residues | ||||
Sequence: ASRKRQHEEPESFFT | ||||||
Compositional bias | 236-289 | Acidic residues | ||||
Sequence: DMDDEEGEAEDDDDDDEEEEGLEDIDEEGDEDEGEEDDDEDEGEEGEEDEGEDD | ||||||
Sequence conflict | 273 | in Ref. 2; AAP92538 | ||||
Sequence: D → N |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S68589 EMBL· GenBank· DDBJ | AAC60681.1 EMBL· GenBank· DDBJ | mRNA | ||
S68987 EMBL· GenBank· DDBJ | AAC60682.1 EMBL· GenBank· DDBJ | mRNA | ||
AY325137 EMBL· GenBank· DDBJ | AAP92538.1 EMBL· GenBank· DDBJ | mRNA |