Q01804 · OTUD4_HUMAN
- ProteinOTU domain-containing protein 4
- GeneOTUD4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1114 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066).
Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111).
Catalytic activity
Activity regulation
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 42 | |||||
Sequence: D | ||||||
Active site | 45 | Nucleophile | ||||
Sequence: C | ||||||
Active site | 148 | |||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Molecular Function | cysteine-type deubiquitinase activity | |
Molecular Function | K63-linked deubiquitinase activity | |
Molecular Function | molecular adaptor activity | |
Molecular Function | RNA binding | |
Biological Process | DNA alkylation repair | |
Biological Process | innate immune response | |
Biological Process | negative regulation of interleukin-1-mediated signaling pathway | |
Biological Process | negative regulation of toll-like receptor signaling pathway | |
Biological Process | protein deubiquitination | |
Biological Process | protein K11-linked deubiquitination | |
Biological Process | protein K48-linked deubiquitination | |
Biological Process | protein K63-linked deubiquitination | |
Biological Process | proteolysis | |
Biological Process | regulation of protein K48-linked deubiquitination |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameOTU domain-containing protein 4
- 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 accessionQ01804
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 45 | Abolishes 'Lys-48'- and 'Lys-63'-specific deubiquitinase activity. Impairs 'Lys-63'-specific deubiquitinase activity toward MYD88 substrate. | ||||
Sequence: C → A | ||||||
Mutagenesis | 45 | Abolishes 'Lys-48'- and 'Lys-63'-specific deubiquitinase activity. | ||||
Sequence: C → S | ||||||
Mutagenesis | 181-550 | Abolishes interaction with USP7 and USP9X deubiquitinases. | ||||
Sequence: Missing | ||||||
Natural variant | VAR_029377 | 194 | in dbSNP:rs36225458 | |||
Sequence: A → G | ||||||
Mutagenesis | 202 | Decreases 'Lys-63'-specific deubiquitinase activity. Loss of 'Lys-63'-specific deubiquitinase activity; when associated with A-204. | ||||
Sequence: S → A | ||||||
Mutagenesis | 204 | Loss of 'Lys-63'-specific deubiquitinase activity; when associated with A-204. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_038848 | 216 | in dbSNP:rs36225838 | |||
Sequence: A → T | ||||||
Mutagenesis | 273-275 | Abolishes 'Lys-63'-specific deubiquitinase activity by impairing the affinity for 'Lys-63'-linked ubiquitin chain substrate. | ||||
Sequence: KRD → AAA | ||||||
Mutagenesis | 279 | Abolishes 'Lys-63'-specific deubiquitinase activity by impairing the affinity for 'Lys-63'-linked ubiquitin chain substrate. | ||||
Sequence: A → R | ||||||
Natural variant | VAR_070050 | 398 | found in patients with cerebellar ataxia and hypogonadotropic hypogonadism; uncertain significance; dbSNP:rs148857745 | |||
Sequence: G → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,241 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 modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000083979 | 1-1114 | UniProt | OTU domain-containing protein 4 | |||
Sequence: MEAAVGVPDGGDQGGAGPREDATPMDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQVEISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYPIKYKESSAMCQSLLYELLYEKVFKTDVSKIVMELDTLEVADEDNSEISDSEDDSCKSKTAAAAADVNGFKPLSGNEQLKNNGNSTSLPLSRKVLKSLNPAVYRNVEYEIWLKSKQAQQKRDYSIAAGLQYEVGDKCQVRLDHNGKFLNADVQGIHSENGPVLVEELGKKHTSKNLKAPPPESWNTVSGKKMKKPSTSGQNFHSDVDYRGPKNPSKPIKAPSALPPRLQHPSGVRQHAFSSHSSGSQSQKFSSEHKNLSRTPSQIIRKPDRERVEDFDHTSRESNYFGLSPEERREKQAIEESRLLYEIQNRDEQAFPALSSSSVNQSASQSSNPCVQRKSSHVGDRKGSRRRMDTEERKDKDSIHGHSQLDKRPEPSTLENITDDKYATVSSPSKSKKLECPSPAEQKPAEHVSLSNPAPLLVSPEVHLTPAVPSLPATVPAWPSEPTTFGPTGVPAPIPVLSVTQTLTTGPDSAVSQAHLTPSPVPVSIQAVNQPLMPLPQTLSLYQDPLYPGFPCNEKGDRAIVPPYSLCQTGEDLPKDKNILRFFFNLGVKAYSCPMWAPHSYLYPLHQAYLAACRMYPKVPVPVYPHNPWFQEAPAAQNESDCTCTDAHFPMQTEASVNGQMPQPEIGPPTFSSPLVIPPSQVSESHGQLSYQADLESETPGQLLHADYEESLSGKNMFPQPSFGPNPFLGPVPIAPPFFPHVWYGYPFQGFIENPVMRQNIVLPSDEKGELDLSLENLDLSKDCGSVSTVDEFPEARGEHVHSLPEASVSSKPDEGRTEQSSQTRKADTALASIPPVAEGKAHPPTQILNRERETVPVELEPKRTIQSLKEKTEKVKDPKTAADVVSPGANSVDSRVQRPKEESSEDENEVSNILRSGRSKQFYNQTYGSRKYKSDWGYSGRGGYQHVRSEESWKGQPSRSRDEGYQYHRNVRGRPFRGDRRRSGMGDGHRGQHT | |||||||
Modified residue | 120 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 126 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 128 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 131 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 166 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 199 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 202 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 204 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 284 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 341 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 349 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 361 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 414 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 439 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 439 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 443 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 443 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 460 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 460 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 545 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 546 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 546 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 557 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 893 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 893 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 900 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 905 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 922 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1006 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1006 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1011 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1011 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1014 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1023 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1023 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1024 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1024 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1031 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1049 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1049 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with ALKBH3; the interaction is direct (PubMed:25944111).
Interacts with USP7; the interaction is direct (PubMed:25944111).
Interacts with USP9X; the interaction is direct (PubMed:25944111).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q01804 | EXOSC8 Q96B26 | 6 | EBI-1054396, EBI-371922 | |
BINARY | Q01804 | REL Q04864 | 3 | EBI-1054396, EBI-307352 | |
BINARY | Q01804 | STAT1 P42224 | 3 | EBI-1054396, EBI-1057697 | |
BINARY | Q01804 | TCF4 P15884 | 3 | EBI-1054396, EBI-533224 | |
BINARY | Q01804 | VDR P11473-2 | 3 | EBI-1054396, EBI-12874016 | |
BINARY | Q01804 | ZNF655 Q8N720 | 3 | EBI-1054396, EBI-625509 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-22 | Disordered | ||||
Sequence: MEAAVGVPDGGDQGGAGPREDA | ||||||
Domain | 34-155 | OTU | ||||
Sequence: LYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQVEISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYPI | ||||||
Region | 39-45 | Cys-loop | ||||
Sequence: VAKDGSC | ||||||
Region | 94-104 | Variable-loop | ||||
Sequence: LENPQEWVGQV | ||||||
Region | 143-148 | His-loop | ||||
Sequence: FSNGNH | ||||||
Region | 323-449 | Disordered | ||||
Sequence: KHTSKNLKAPPPESWNTVSGKKMKKPSTSGQNFHSDVDYRGPKNPSKPIKAPSALPPRLQHPSGVRQHAFSSHSSGSQSQKFSSEHKNLSRTPSQIIRKPDRERVEDFDHTSRESNYFGLSPEERRE | ||||||
Compositional bias | 342-357 | Polar residues | ||||
Sequence: GKKMKKPSTSGQNFHS | ||||||
Compositional bias | 387-417 | Polar residues | ||||
Sequence: VRQHAFSSHSSGSQSQKFSSEHKNLSRTPSQ | ||||||
Compositional bias | 418-449 | Basic and acidic residues | ||||
Sequence: IIRKPDRERVEDFDHTSRESNYFGLSPEERRE | ||||||
Compositional bias | 472-493 | Polar residues | ||||
Sequence: ALSSSSVNQSASQSSNPCVQRK | ||||||
Region | 472-567 | Disordered | ||||
Sequence: ALSSSSVNQSASQSSNPCVQRKSSHVGDRKGSRRRMDTEERKDKDSIHGHSQLDKRPEPSTLENITDDKYATVSSPSKSKKLECPSPAEQKPAEHV | ||||||
Compositional bias | 494-534 | Basic and acidic residues | ||||
Sequence: SSHVGDRKGSRRRMDTEERKDKDSIHGHSQLDKRPEPSTLE | ||||||
Compositional bias | 536-552 | Polar residues | ||||
Sequence: ITDDKYATVSSPSKSKK | ||||||
Region | 911-1114 | Disordered | ||||
Sequence: EFPEARGEHVHSLPEASVSSKPDEGRTEQSSQTRKADTALASIPPVAEGKAHPPTQILNRERETVPVELEPKRTIQSLKEKTEKVKDPKTAADVVSPGANSVDSRVQRPKEESSEDENEVSNILRSGRSKQFYNQTYGSRKYKSDWGYSGRGGYQHVRSEESWKGQPSRSRDEGYQYHRNVRGRPFRGDRRRSGMGDGHRGQHT | ||||||
Compositional bias | 973-1000 | Basic and acidic residues | ||||
Sequence: ETVPVELEPKRTIQSLKEKTEKVKDPKT | ||||||
Compositional bias | 1015-1033 | Basic and acidic residues | ||||
Sequence: RVQRPKEESSEDENEVSNI | ||||||
Compositional bias | 1034-1052 | Polar residues | ||||
Sequence: LRSGRSKQFYNQTYGSRKY | ||||||
Compositional bias | 1072-1114 | Basic and acidic residues | ||||
Sequence: SWKGQPSRSRDEGYQYHRNVRGRPFRGDRRRSGMGDGHRGQHT |
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q01804-1
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
- Length1,114
- Mass (Da)124,045
- Last updated2014-03-19 v4
- ChecksumAD8DF5FEAB8CBE32
Q01804-5
- Name2
Q01804-3
- Name3
- Differences from canonical
- 1-65: Missing
Q01804-4
- Name4
- NotePredicted from a chimeric transcript isolated from HIV-1-infected cells. The premature stop may be due to intron retention.
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_038830 | 1-65 | in isoform 2, isoform 3 and isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_021671 | 211-1114 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_053825 | 231 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 342-357 | Polar residues | ||||
Sequence: GKKMKKPSTSGQNFHS | ||||||
Compositional bias | 387-417 | Polar residues | ||||
Sequence: VRQHAFSSHSSGSQSQKFSSEHKNLSRTPSQ | ||||||
Compositional bias | 418-449 | Basic and acidic residues | ||||
Sequence: IIRKPDRERVEDFDHTSRESNYFGLSPEERRE | ||||||
Compositional bias | 472-493 | Polar residues | ||||
Sequence: ALSSSSVNQSASQSSNPCVQRK | ||||||
Compositional bias | 494-534 | Basic and acidic residues | ||||
Sequence: SSHVGDRKGSRRRMDTEERKDKDSIHGHSQLDKRPEPSTLE | ||||||
Compositional bias | 536-552 | Polar residues | ||||
Sequence: ITDDKYATVSSPSKSKK | ||||||
Sequence conflict | 809 | in Ref. 1; BAB71229 | ||||
Sequence: S → P | ||||||
Sequence conflict | 915 | in Ref. 9; CAB70748 | ||||
Sequence: A → S | ||||||
Compositional bias | 973-1000 | Basic and acidic residues | ||||
Sequence: ETVPVELEPKRTIQSLKEKTEKVKDPKT | ||||||
Compositional bias | 1015-1033 | Basic and acidic residues | ||||
Sequence: RVQRPKEESSEDENEVSNI | ||||||
Compositional bias | 1034-1052 | Polar residues | ||||
Sequence: LRSGRSKQFYNQTYGSRKY | ||||||
Compositional bias | 1072-1114 | Basic and acidic residues | ||||
Sequence: SWKGQPSRSRDEGYQYHRNVRGRPFRGDRRRSGMGDGHRGQHT |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK056597 EMBL· GenBank· DDBJ | BAB71229.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK302581 EMBL· GenBank· DDBJ | BAG63836.1 EMBL· GenBank· DDBJ | mRNA | ||
AC096757 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471056 EMBL· GenBank· DDBJ | EAX05045.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471056 EMBL· GenBank· DDBJ | EAX05046.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X68242 EMBL· GenBank· DDBJ | CAA48313.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ427109 EMBL· GenBank· DDBJ | ABD72605.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC057242 EMBL· GenBank· DDBJ | AAH57242.2 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
BC118572 EMBL· GenBank· DDBJ | AAI18573.1 EMBL· GenBank· DDBJ | mRNA | ||
BC118653 EMBL· GenBank· DDBJ | AAI18654.1 EMBL· GenBank· DDBJ | mRNA | ||
AB028969 EMBL· GenBank· DDBJ | BAA82998.2 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AL137460 EMBL· GenBank· DDBJ | CAB70748.1 EMBL· GenBank· DDBJ | mRNA |