Q86UK7 · ZN598_HUMAN
- ProteinE3 ubiquitin-protein ligase ZNF598
- GeneZNF598
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids904 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, leading to degradation of nascent peptide chains (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:32099016, PubMed:32579943, PubMed:33581075).
ZNF598 is activated when ribosomes are stalled within an mRNA following translation of prematurely polyadenylated mRNAs (PubMed:28065601, PubMed:28132843, PubMed:28685749).
Acts as a ribosome collision sensor: specifically recognizes and binds collided di-ribosome, which arises when a trailing ribosome encounters a slower leading ribosome, leading to terminally arrest translation (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:30293783).
Following binding to colliding ribosomes, mediates monoubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS3/uS3, and 'Lys-63'-linked polyubiquitination of RPS20/uS10 (PubMed:28065601, PubMed:28132843, PubMed:28685749).
Polyubiquitination of RPS20/uS10 promotes recruitment of the RQT (ribosome quality control trigger) complex, which drives the disassembly of stalled ribosomes, followed by degradation of nascent peptides (PubMed:32099016, PubMed:32579943, PubMed:36302773).
E3 ubiquitin-protein ligase activity is dependent on the E2 ubiquitin-conjugating enzyme UBE2D3 (PubMed:28685749).
Also acts as an adapter that recruits the 4EHP-GYF2 complex to mRNAs (PubMed:22751931, PubMed:32726578).
Independently of its role in RQC, may also act as a negative regulator of interferon-stimulated gene (ISG) expression (PubMed:29719242).
ZNF598 is activated when ribosomes are stalled within an mRNA following translation of prematurely polyadenylated mRNAs (PubMed:28065601, PubMed:28132843, PubMed:28685749).
Acts as a ribosome collision sensor: specifically recognizes and binds collided di-ribosome, which arises when a trailing ribosome encounters a slower leading ribosome, leading to terminally arrest translation (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:30293783).
Following binding to colliding ribosomes, mediates monoubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS3/uS3, and 'Lys-63'-linked polyubiquitination of RPS20/uS10 (PubMed:28065601, PubMed:28132843, PubMed:28685749).
Polyubiquitination of RPS20/uS10 promotes recruitment of the RQT (ribosome quality control trigger) complex, which drives the disassembly of stalled ribosomes, followed by degradation of nascent peptides (PubMed:32099016, PubMed:32579943, PubMed:36302773).
E3 ubiquitin-protein ligase activity is dependent on the E2 ubiquitin-conjugating enzyme UBE2D3 (PubMed:28685749).
Also acts as an adapter that recruits the 4EHP-GYF2 complex to mRNAs (PubMed:22751931, PubMed:32726578).
Independently of its role in RQC, may also act as a negative regulator of interferon-stimulated gene (ISG) expression (PubMed:29719242).
(Microbial infection) Required for poxvirus protein synthesis by mediating ubiquitination of RPS10/eS10 and RPS20/uS10 (PubMed:29719242).
Poxvirus encoding mRNAs contain unusual 5' poly(A) leaders and ZNF598 is required for their translational efficiency, possibly via its ability to suppress readthrough or sliding on shorter poly(A) tracts (PubMed:29719242).
Poxvirus encoding mRNAs contain unusual 5' poly(A) leaders and ZNF598 is required for their translational efficiency, possibly via its ability to suppress readthrough or sliding on shorter poly(A) tracts (PubMed:29719242).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | cytosolic ribosome | |
Molecular Function | metal ion binding | |
Molecular Function | protein-RNA adaptor activity | |
Molecular Function | ribosome binding | |
Molecular Function | RNA binding | |
Molecular Function | stalled ribosome sensor activity | |
Molecular Function | ubiquitin protein ligase activity | |
Biological Process | negative regulation of translational initiation | |
Biological Process | protein K63-linked ubiquitination | |
Biological Process | protein monoubiquitination | |
Biological Process | protein ubiquitination | |
Biological Process | rescue of stalled ribosome | |
Biological Process | ribosome-associated ubiquitin-dependent protein catabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase ZNF598
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ86UK7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 29 | Abolishes E3 ubiquitin-protein ligase activity, leading to enhanced readthrough on the poly(A)-stall sequences. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_034470 | 453 | in dbSNP:rs11556528 | |||
Sequence: S → Y | ||||||
Natural variant | VAR_059818 | 608 | in dbSNP:rs11248905 | |||
Sequence: A → T | ||||||
Natural variant | VAR_052147 | 637 | in dbSNP:rs2286469 | |||
Sequence: T → M | ||||||
Natural variant | VAR_034471 | 725 | in dbSNP:rs2286468 | |||
Sequence: C → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 4 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 chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000250568 | 1-904 | UniProt | E3 ubiquitin-protein ligase ZNF598 | |||
Sequence: MAAAGGAEGRRAALEAAAAAAPERGGGSCVLCCGDLEATALGRCDHPVCYRCSTKMRVLCEQRYCAVCREELRQVVFGKKLPAFATIPIHQLQHEKKYDIYFADGKVYALYRQLLQHECPRCPELPPFSLFGDLEQHMRRQHELFCCRLCLQHLQIFTYERKWYSRKDLARHRMQGDPDDTSHRGHPLCKFCDERYLDNDELLKHLRRDHYFCHFCDSDGAQDYYSDYAYLREHFREKHFLCEEGRCSTEQFTHAFRTEIDLKAHRTACHSRSRAEARQNRHIDLQFSYAPRHSRRNEGVVGGEDYEEVDRYSRQGRVARAGTRGAQQSRRGSWRYKREEEDREVAAAVRASVAAQQQEEARRSEDQEEGGRPKKEEAAARGPEDPRGPRRSPRTQGEGPGPKETSTNGPVSQEAFSVTGPAAPGCVGVPGALPPPSPKLKDEDFPSLSASTSSSCSTAATPGPVGLALPYAIPARGRSAFQEEDFPALVSSVPKPGTAPTSLVSAWNSSSSSKKVAQPPLSAQATGSGQPTRKAGKGSRGGRKGGPPFTQEEEEDGGPALQELLSTRPTGSVSSTLGLASIQPSKVGKKKKVGSEKPGTTLPQPPPATCPPGALQAPEAPASRAEGPVAVVVNGHTEGPAPARSAPKEPPGLPRPLGSFPCPTPQEDFPALGGPCPPRMPPPPGFSAVVLLKGTPPPPPPGLVPPISKPPPGFSGLLPSPHPACVPSPATTTTTKAPRLLPAPRAYLVPENFRERNLQLIQSIRDFLQSDEARFSEFKSHSGEFRQGLISAAQYYKSCRDLLGENFQKVFNELLVLLPDTAKQQELLSAHTDFCNREKPLSTKSKKNKKSAWQATTQQAGLDCRVCPTCQQVLAHGDASSHQALHAARDDDFPSLQAIARIIT | |||||||
Modified residue | 306 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 306 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 428 | UniProt | In isoform Q86UK7-2; Phosphoserine | ||||
Sequence: G | |||||||
Modified residue | 431 | UniProt | In isoform Q86UK7-3; Phosphoserine | ||||
Sequence: G | |||||||
Modified residue | 437 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 437 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 461 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 479 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 502 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 511 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 512 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 528 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 695 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 720 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 728 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with the E2 ubiquitin-conjugating enzyme UBE2D3 (PubMed:28685749).
Component of the 4EHP-GYF2 complex, at least composed of EIF4E2, GIGYF2 and ZNF598 (PubMed:22751931, PubMed:32726578).
Component of the 4EHP-GYF2 complex, at least composed of EIF4E2, GIGYF2 and ZNF598 (PubMed:22751931, PubMed:32726578).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q86UK7 | GIGYF1 O75420 | 2 | EBI-719433, EBI-947774 | |
BINARY | Q86UK7 | YWHAE P62258 | 3 | EBI-719433, EBI-356498 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for zinc finger, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 29-69 | RING-type | ||||
Sequence: CVLCCGDLEATALGRCDHPVCYRCSTKMRVLCEQRYCAVCR | ||||||
Zinc finger | 187-210 | C2H2-type | ||||
Sequence: PLCKFCDERYLDNDELLKHLRRDH | ||||||
Region | 312-469 | Disordered | ||||
Sequence: YSRQGRVARAGTRGAQQSRRGSWRYKREEEDREVAAAVRASVAAQQQEEARRSEDQEEGGRPKKEEAAARGPEDPRGPRRSPRTQGEGPGPKETSTNGPVSQEAFSVTGPAAPGCVGVPGALPPPSPKLKDEDFPSLSASTSSSCSTAATPGPVGLAL | ||||||
Compositional bias | 332-347 | Basic and acidic residues | ||||
Sequence: GSWRYKREEEDREVAA | ||||||
Compositional bias | 359-392 | Basic and acidic residues | ||||
Sequence: EEARRSEDQEEGGRPKKEEAAARGPEDPRGPRRS | ||||||
Compositional bias | 399-415 | Polar residues | ||||
Sequence: GPGPKETSTNGPVSQEA | ||||||
Compositional bias | 446-461 | Polar residues | ||||
Sequence: PSLSASTSSSCSTAAT | ||||||
Region | 490-656 | Disordered | ||||
Sequence: VSSVPKPGTAPTSLVSAWNSSSSSKKVAQPPLSAQATGSGQPTRKAGKGSRGGRKGGPPFTQEEEEDGGPALQELLSTRPTGSVSSTLGLASIQPSKVGKKKKVGSEKPGTTLPQPPPATCPPGALQAPEAPASRAEGPVAVVVNGHTEGPAPARSAPKEPPGLPRP | ||||||
Compositional bias | 495-533 | Polar residues | ||||
Sequence: KPGTAPTSLVSAWNSSSSSKKVAQPPLSAQATGSGQPTR | ||||||
Compositional bias | 565-582 | Polar residues | ||||
Sequence: LSTRPTGSVSSTLGLASI | ||||||
Compositional bias | 600-614 | Pro residues | ||||
Sequence: TTLPQPPPATCPPGA |
Sequence similarities
Belongs to the ZNF598/HEL2 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q86UK7-1
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
- Length904
- Mass (Da)98,637
- Last updated2003-06-01 v1
- Checksum492F67EE4E334743
Q86UK7-2
- Name2
Q86UK7-3
- Name3
- Differences from canonical
- 424-429: Missing
Q86UK7-4
- Name4
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0AAG2UWE8 | A0AAG2UWE8_HUMAN | ZNF598 | 904 | ||
H3BR87 | H3BR87_HUMAN | ZNF598 | 203 | ||
H3BPG6 | H3BPG6_HUMAN | ZNF598 | 904 | ||
H3BPF3 | H3BPF3_HUMAN | ZNF598 | 259 |
Sequence caution
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_020660 | 1-397 | in isoform 4 | |||
Sequence: Missing | ||||||
Compositional bias | 332-347 | Basic and acidic residues | ||||
Sequence: GSWRYKREEEDREVAA | ||||||
Alternative sequence | VSP_020661 | 335-337 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 359-392 | Basic and acidic residues | ||||
Sequence: EEARRSEDQEEGGRPKKEEAAARGPEDPRGPRRS | ||||||
Alternative sequence | VSP_020662 | 398-431 | in isoform 4 | |||
Sequence: EGPGPKETSTNGPVSQEAFSVTGPAAPGCVGVPG → MVGGCGQPQVGAGRAGMEPRGLIAVDQLCFPAPS | ||||||
Compositional bias | 399-415 | Polar residues | ||||
Sequence: GPGPKETSTNGPVSQEA | ||||||
Alternative sequence | VSP_020663 | 424-429 | in isoform 2 and isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 446-461 | Polar residues | ||||
Sequence: PSLSASTSSSCSTAAT | ||||||
Compositional bias | 495-533 | Polar residues | ||||
Sequence: KPGTAPTSLVSAWNSSSSSKKVAQPPLSAQATGSGQPTR | ||||||
Alternative sequence | VSP_020664 | 551 | in isoform 2 and isoform 4 | |||
Sequence: Q → QE | ||||||
Compositional bias | 565-582 | Polar residues | ||||
Sequence: LSTRPTGSVSSTLGLASI | ||||||
Compositional bias | 600-614 | Pro residues | ||||
Sequence: TTLPQPPPATCPPGA | ||||||
Alternative sequence | VSP_020665 | 738-904 | in isoform 4 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK024487 EMBL· GenBank· DDBJ | BAB15777.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC010990 EMBL· GenBank· DDBJ | AAH10990.2 EMBL· GenBank· DDBJ | mRNA | ||
BC041015 EMBL· GenBank· DDBJ | AAH41015.1 EMBL· GenBank· DDBJ | mRNA | ||
BC050477 EMBL· GenBank· DDBJ | AAH50477.1 EMBL· GenBank· DDBJ | mRNA | ||
AL834428 EMBL· GenBank· DDBJ | CAD39089.1 EMBL· GenBank· DDBJ | mRNA |