Q9GZS3 · SKI8_HUMAN
- ProteinSuperkiller complex protein 8
- GeneSKIC8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids305 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1 (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C is required for transcription of Hox and Wnt target genes (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3) (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors (PubMed:16307923, PubMed:19952111, PubMed:20178742).
In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742).
Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3), dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742).
Also acts as a component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways (PubMed:16024656, PubMed:32006463, PubMed:35120588).
The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation (PubMed:32006463, PubMed:35120588).
SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling (PubMed:32006463).
PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1 (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C is required for transcription of Hox and Wnt target genes (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3) (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742).
PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors (PubMed:16307923, PubMed:19952111, PubMed:20178742).
In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742).
Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3), dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742).
Also acts as a component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways (PubMed:16024656, PubMed:32006463, PubMed:35120588).
The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation (PubMed:32006463, PubMed:35120588).
SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling (PubMed:32006463).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | Cdc73/Paf1 complex | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | euchromatin | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | Ski complex | |
Biological Process | negative regulation of myeloid cell differentiation | |
Biological Process | nuclear-transcribed mRNA catabolic process, 3'-5' exonucleolytic nonsense-mediated decay | |
Biological Process | rescue of stalled ribosome | |
Biological Process | transcription elongation by RNA polymerase II | |
Biological Process | Wnt signaling pathway |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSuperkiller complex protein 8
- Short namesSki8
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9GZS3
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 262 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed; alternate | ||||
Sequence: M | ||||||
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000425748 | 1-305 | Superkiller complex protein 8 | |||
Sequence: MTNQYGILFKQEQAHDDAIWSVAWGTNKKENSETVVTGSLDDLVKVWKWRDERLDLQWSLEGHQLGVVSVDISHTLPIAASSSLDAHIRLWDLENGKQIKSIDAGPVDAWTLAFSPDSQYLATGTHVGKVNIFGVESGKKEYSLDTRGKFILSIAYSPDGKYLASGAIDGIINIFDIATGKLLHTLEGHAMPIRSLTFSPDSQLLVTASDDGYIKIYDVQHANLAGTLSGHASWVLNVAFCPDDTHFVSSSSDKSVKVWDVGTRTCVHTFFDHQDQVWGVKYNGNGSKIVSVGDDQEIHIYDCPI | ||||||
Modified residue | 2 | N-acetylthreonine; in WD repeat-containing protein 61, N-terminally processed | ||||
Sequence: T | ||||||
Chain | PRO_0000245851 | 2-305 | Superkiller complex protein 8, N-terminally processed | |||
Sequence: TNQYGILFKQEQAHDDAIWSVAWGTNKKENSETVVTGSLDDLVKVWKWRDERLDLQWSLEGHQLGVVSVDISHTLPIAASSSLDAHIRLWDLENGKQIKSIDAGPVDAWTLAFSPDSQYLATGTHVGKVNIFGVESGKKEYSLDTRGKFILSIAYSPDGKYLASGAIDGIINIFDIATGKLLHTLEGHAMPIRSLTFSPDSQLLVTASDDGYIKIYDVQHANLAGTLSGHASWVLNVAFCPDDTHFVSSSSDKSVKVWDVGTRTCVHTFFDHQDQVWGVKYNGNGSKIVSVGDDQEIHIYDCPI |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8 (PubMed:16024656, PubMed:19952111, PubMed:20178742).
The PAF1 complex interacts with PHF5A (By similarity).
Within the PAF1 complex interacts directly with PHF5A (By similarity).
Component of the SKI complex which consists of SKIC2, SKIC3 and SKIC8 (PubMed:16024656, PubMed:32006463, PubMed:35120588).
The PAF1 complex interacts with PHF5A (By similarity).
Within the PAF1 complex interacts directly with PHF5A (By similarity).
Component of the SKI complex which consists of SKIC2, SKIC3 and SKIC8 (PubMed:16024656, PubMed:32006463, PubMed:35120588).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 14-57 | WD 1 | ||||
Sequence: AHDDAIWSVAWGTNKKENSETVVTGSLDDLVKVWKWRDERLDLQ | ||||||
Repeat | 62-101 | WD 2 | ||||
Sequence: GHQLGVVSVDISHTLPIAASSSLDAHIRLWDLENGKQIKS | ||||||
Repeat | 104-143 | WD 3 | ||||
Sequence: AGPVDAWTLAFSPDSQYLATGTHVGKVNIFGVESGKKEYS | ||||||
Repeat | 146-187 | WD 4 | ||||
Sequence: TRGKFILSIAYSPDGKYLASGAIDGIINIFDIATGKLLHTLE | ||||||
Repeat | 188-227 | WD 5 | ||||
Sequence: GHAMPIRSLTFSPDSQLLVTASDDGYIKIYDVQHANLAGT | ||||||
Repeat | 230-269 | WD 6 | ||||
Sequence: GHASWVLNVAFCPDDTHFVSSSSDKSVKVWDVGTRTCVHT | ||||||
Repeat | 272-305 | WD 7 | ||||
Sequence: DHQDQVWGVKYNGNGSKIVSVGDDQEIHIYDCPI |
Sequence similarities
Belongs to the SKI8 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length305
- Mass (Da)33,581
- Last updated2001-03-01 v1
- ChecksumA26C4BBD4F8ADB80
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 91 | in Ref. 2; AAP97249 | ||||
Sequence: W → R | ||||||
Sequence conflict | 176 | in Ref. 2; AAP97249 | ||||
Sequence: D → A | ||||||
Sequence conflict | 229 | in Ref. 4; CAG33614 | ||||
Sequence: S → G | ||||||
Sequence conflict | 255 | in Ref. 4; CAG33614 | ||||
Sequence: S → N | ||||||
Sequence conflict | 259 | in Ref. 2; AAP97249 | ||||
Sequence: W → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF309553 EMBL· GenBank· DDBJ | AAG31639.1 EMBL· GenBank· DDBJ | mRNA | ||
AF100786 EMBL· GenBank· DDBJ | AAP97225.1 EMBL· GenBank· DDBJ | mRNA | ||
AF127799 EMBL· GenBank· DDBJ | AAP97249.1 EMBL· GenBank· DDBJ | mRNA | ||
AK024754 EMBL· GenBank· DDBJ | BAB14986.1 EMBL· GenBank· DDBJ | mRNA | ||
CR457333 EMBL· GenBank· DDBJ | CAG33614.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471136 EMBL· GenBank· DDBJ | EAW99174.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471136 EMBL· GenBank· DDBJ | EAW99175.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC010080 EMBL· GenBank· DDBJ | AAH10080.1 EMBL· GenBank· DDBJ | mRNA |