P47050 · CUL8_YEAST
- ProteinCullin-8
- GeneRTT101
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids842 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes (CRLs), which mediate the ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The CRL associates with CDC34 as the E2 ubiquitin-conjugating enzyme. The functional specificity of the CRL depends on the type of the associated substrate receptor protein. RTT101(MMS1-MMS22) promotes fork progression through damaged DNA or natural pause sites by stabilizing replication proteins like the replication fork-pausing complex (FPC) and leading-strand polymerase at stalled replication forks. RTT101(MMS1-MMS22) ubiquitinates the acetylated histones H3K56ac-H4 at lysine residues H3K121, H3K122 and H3K125. Ubiquitination is required for efficient histone deposition during replication-coupled nucleosome assembly, probably by facilitating the transfer of H3-H4 from ASF1 to other chaperones involved in histone deposition. RTT101(MMS1-CRT10) may regulate nucleotide synthesis through transcriptional regulation of ribonucleotide reductase. RTT101(MMS1) is also involved in the non-functional rRNA decay (NRD) of 25S rRNA through the selective, ubiquitination-dependent degradation of nonfunctional ribosomal particles. Ubiquitinates the FACT (facilitates chromatin transcription) complex subunit SPT16 in an MMS1-independent manner. Involved in regulation of Ty1 transposition and protects the genome from Ty1 integration upstream of tRNA genes.
Pathway
Protein modification; protein ubiquitination.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | Cul3-RING ubiquitin ligase complex | |
Cellular Component | Cul8-RING ubiquitin ligase complex | |
Cellular Component | cytoplasm | |
Cellular Component | nucleus | |
Molecular Function | ubiquitin protein ligase binding | |
Molecular Function | ubiquitin-protein transferase activity | |
Biological Process | cell division | |
Biological Process | DNA repair | |
Biological Process | heterochromatin formation | |
Biological Process | nonfunctional rRNA decay | |
Biological Process | nucleosome assembly | |
Biological Process | protein ubiquitination | |
Biological Process | regulation of DNA replication | |
Biological Process | regulation of mitotic nuclear division | |
Biological Process | replication fork processing | |
Biological Process | retrotransposon silencing |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCullin-8
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Saccharomyces
Accessions
- Primary accessionP47050
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Delays anaphase progression.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 680-686 | Disrupts interaction with HRT1 and prevents RUB1/NEDD8 modification. | ||||
Sequence: Missing | ||||||
Mutagenesis | 791 | Prevents RUB1/NEDD8 modification. | ||||
Sequence: K → A or R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 22 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000119807 | 1-842 | Cullin-8 | |||
Sequence: MINESVSKREGFHESISRETSASNALGLYNKFNDERNPRYRTMIAELHEFFHLTLAETITETDVKELECNKEKAAKFRKLMPKMLNNCRELTQRKSYIPYNSEFNGNDEKQKKFQLLHQHQIVLSFQEFCDELAKLIIDAHVLSFLTRCDYSYEIIPKNWTSFYKLFQYVMGAVGPIISYVPVNYPMIRKELGFETLTIFQYYDSKLFECMKSHFGREFSTLVSATIHHYIHMFPITNTMLEKEVPMLRIMSNCNFSIEGLSPKDFYMKTLRQYYCEESNLRPRLETFKNFKVLLTRNALLASLFSPEWVSDANDLFISHLLLNKKSISEYIEIGKDTYDEEKERYFKTETHFSLLMFRNAFEAKNMLSKFKEFCDDAVSEKLKAAYGSNHDTERLFDEVVQLANVDHLKIYSDSIEYHLCNLLGSTSKAIEQYVKYFESHLFIIVRKIKTTKKDLPRDMKIKYLNENLPILRLKFVNLPTFPNFFERSIFRKTILQSDQNSSFIKDILPVYKDSLMELFKQRIITNVSQEDEMRYRDQYQPYLSQFFQPVEVMADLRIKYASFLSFYENIEAAVKFGKTYNENNSKSFFPLIFDRERIPKVFQQSNEVKKNFVLPQEMDDTWNQFLRNYHEQNKVEDSDASKKELYPMWNLHHCEVESPYIIQDGTNLIFELTLFQTCVLTLFNESDHLTLQVISEQTKLAYKDLALVLKSFCNYKILTRDIDNTYSINESFKPDMKKVKNGKLRVVLPRTASLQSSNTGGERTSSAHHEGSNSQWTQELLKACITRSVKSERNGLDYDHLFETVKQQIKGFSVGEFKDALAKLLRDKFITRDESTATYKY | ||||||
Cross-link | 791 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) | ||||
Sequence: K |
Post-translational modification
Neddylated. HRT1-binding is necessary for RUB1/NEDD8 modification of RTT101. The modification enhances ubiquitin-ligase activity.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Component of multiple cullin-RING ligases (CRLs) composed of 4 subunits: the RING protein HRT1, the cullin RTT101, a linker protein MMS1, and one of many alternative substrate receptors belonging to a protein family described as DCAF (DDB1- and CUL4-associated factor). Component of a RTT101(MMS1-MMS22) complex with the substrate receptor MMS22. This complex further interacts with RTT107 and CTF4 to form RTT101-MMS1-MMS22-RTT107 and RTT101-MMS1-MMS22-CTF4 complexes respectively. Component of a RTT101(MSS1-CRT10) complex with the substrate receptor CRT10. Component of a RTT101(MSS1-ESC2) complex with the potential substrate receptor ESC2. Component of a RTT101(MSS1-ORC5) complex with the potential substrate receptor ORC5. Interacts (via C-ter) with HRT1; required for ubiquitin-ligase activity. Interacts (via N-ter) with MMS1.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P47050 | CDC34 P14682 | 2 | EBI-25861, EBI-19730 | |
BINARY | P47050 | CRT10 Q08226 | 2 | EBI-25861, EBI-30025 | |
BINARY | P47050 | ESC2 Q06340 | 4 | EBI-25861, EBI-33799 | |
BINARY | P47050 | HRT1 Q08273 | 3 | EBI-25861, EBI-31686 | |
BINARY | P47050 | MMS1 Q06211 | 13 | EBI-25861, EBI-38894 | |
BINARY | P47050 | MMS22 Q06164 | 11 | EBI-25861, EBI-31156 | |
BINARY | P47050 | ORC5 P50874 | 3 | EBI-25861, EBI-12584 | |
BINARY | P47050 | RTT107 P38850 | 5 | EBI-25861, EBI-24788 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-50 | Required for interaction with MMS1 | ||||
Sequence: MINESVSKREGFHESISRETSASNALGLYNKFNDERNPRYRTMIAELHEF | ||||||
Region | 755-775 | Disordered | ||||
Sequence: LQSSNTGGERTSSAHHEGSNS |
Sequence similarities
Belongs to the cullin family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length842
- Mass (Da)99,326
- Last updated1996-02-01 v1
- ChecksumA86A48F6DC6AF163
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY387707 EMBL· GenBank· DDBJ | AAQ91376.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z49322 EMBL· GenBank· DDBJ | CAA89338.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK006943 EMBL· GenBank· DDBJ | DAA08753.1 EMBL· GenBank· DDBJ | Genomic DNA |