Q01804 · OTUD4_HUMAN

  • Protein
    OTU domain-containing protein 4
  • Gene
    OTUD4
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066).
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).

Caution

When expressed in bacteria, recombinant OTUD4 specifically hydrolyzes 'Lys-48'-linked diubiquitin. The physiological relevance of this activity remains unknown (PubMed:23827681, PubMed:25944111, PubMed:29395066).
In vivo deubiquitinates 'Lys-63'-linked ubiquitin chains (PubMed:29395066).

Catalytic activity

  • Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
    EC:3.4.19.12 (UniProtKB | ENZYME | Rhea)

Activity regulation

Phosphorylation on Ser-202 and Ser-204 induces 'Lys-63'-specific deubiquitinase activity.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site42
Active site45Nucleophile
Active site148

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentnucleus
Molecular Functioncysteine-type deubiquitinase activity
Molecular FunctionK63-linked deubiquitinase activity
Molecular Functionmolecular adaptor activity
Molecular FunctionRNA binding
Biological ProcessDNA alkylation repair
Biological Processinnate immune response
Biological Processnegative regulation of interleukin-1-mediated signaling pathway
Biological Processnegative regulation of toll-like receptor signaling pathway
Biological Processprotein deubiquitination
Biological Processprotein K11-linked deubiquitination
Biological Processprotein K48-linked deubiquitination
Biological Processprotein K63-linked deubiquitination
Biological Processproteolysis
Biological Processregulation of protein K48-linked deubiquitination

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    OTU domain-containing protein 4
  • EC number
  • Alternative names
    • HIV-1-induced protein HIN-1

Gene names

    • Name
      OTUD4
    • Synonyms
      HIN-1
      , KIAA1046

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q01804
  • Secondary accessions
    • B4DYS4
    • Q147U2
    • Q1ZYK1
    • Q6PG39
    • Q96MQ5

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus
Note: Primarily cytoplasmic.

Keywords

Disease & Variants

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis45Abolishes 'Lys-48'- and 'Lys-63'-specific deubiquitinase activity. Impairs 'Lys-63'-specific deubiquitinase activity toward MYD88 substrate.
Mutagenesis45Abolishes 'Lys-48'- and 'Lys-63'-specific deubiquitinase activity.
Mutagenesis181-550Abolishes interaction with USP7 and USP9X deubiquitinases.
Natural variantVAR_029377194in dbSNP:rs36225458
Mutagenesis202Decreases 'Lys-63'-specific deubiquitinase activity. Loss of 'Lys-63'-specific deubiquitinase activity; when associated with A-204.
Mutagenesis204Loss of 'Lys-63'-specific deubiquitinase activity; when associated with A-204.
Natural variantVAR_038848216in dbSNP:rs36225838
Mutagenesis273-275Abolishes 'Lys-63'-specific deubiquitinase activity by impairing the affinity for 'Lys-63'-linked ubiquitin chain substrate.
Mutagenesis279Abolishes 'Lys-63'-specific deubiquitinase activity by impairing the affinity for 'Lys-63'-linked ubiquitin chain substrate.
Natural variantVAR_070050398found in patients with cerebellar ataxia and hypogonadotropic hypogonadism; uncertain significance; dbSNP:rs148857745

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.

Go to variant viewer

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for modified residue, chain, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
Modified residue1UniProtN-acetylmethionine
ChainPRO_00000839791-1114UniProtOTU domain-containing protein 4
Modified residue120UniProtPhosphotyrosine
Modified residue126UniProtPhosphoserine
Modified residue128UniProtPhosphoserine
Modified residue131UniProtPhosphothreonine
Modified residue166UniProtPhosphoserine
Modified residue199UniProtPhosphoserine
Modified residue202UniProtPhosphoserine
Modified residue204UniProtPhosphoserine
Modified residue (large scale data)284PRIDEPhosphotyrosine
Modified residue341UniProtPhosphoserine
Modified residue (large scale data)349PRIDEPhosphoserine
Modified residue (large scale data)361PRIDEPhosphotyrosine
Modified residue (large scale data)414PRIDEPhosphothreonine
Modified residue439UniProtPhosphotyrosine
Modified residue (large scale data)439PRIDEPhosphotyrosine
Modified residue443UniProtPhosphoserine
Modified residue (large scale data)443PRIDEPhosphoserine
Modified residue460UniProtPhosphotyrosine
Modified residue (large scale data)460PRIDEPhosphotyrosine
Modified residue (large scale data)545PRIDEPhosphoserine
Modified residue546UniProtPhosphoserine
Modified residue (large scale data)546PRIDEPhosphoserine
Modified residue (large scale data)557PRIDEPhosphoserine
Modified residue893UniProtPhosphoserine
Modified residue (large scale data)893PRIDEPhosphoserine
Modified residue900UniProtPhosphoserine
Modified residue (large scale data)905PRIDEPhosphoserine
Modified residue (large scale data)922PRIDEPhosphoserine
Modified residue1006UniProtPhosphoserine
Modified residue (large scale data)1006PRIDEPhosphoserine
Modified residue1011UniProtPhosphoserine
Modified residue (large scale data)1011PRIDEPhosphoserine
Modified residue1014UniProtPhosphoserine
Modified residue1023UniProtPhosphoserine
Modified residue (large scale data)1023PRIDEPhosphoserine
Modified residue1024UniProtPhosphoserine
Modified residue (large scale data)1024PRIDEPhosphoserine
Modified residue (large scale data)1031PRIDEPhosphoserine
Modified residue1049UniProtPhosphoserine
Modified residue (large scale data)1049PRIDEPhosphoserine

Post-translational modification

Phosphorylated on Ser-202 and Ser-204 likely by CSNK2A1-CSNK2A2 serine/threonine-protein kinase complex. Activates 'Lys-63'-specific deubiquitinase activity.

Keywords

Proteomic databases

PTM databases

Expression

Induction

By HIV-1 insertion.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with MYD88; the interaction is direct (PubMed:29395066).
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

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, domain, compositional bias.

TypeIDPosition(s)Description
Region1-22Disordered
Domain34-155OTU
Region39-45Cys-loop
Region94-104Variable-loop
Region143-148His-loop
Region323-449Disordered
Compositional bias342-357Polar residues
Compositional bias387-417Polar residues
Compositional bias418-449Basic and acidic residues
Compositional bias472-493Polar residues
Region472-567Disordered
Compositional bias494-534Basic and acidic residues
Compositional bias536-552Polar residues
Region911-1114Disordered
Compositional bias973-1000Basic and acidic residues
Compositional bias1015-1033Basic and acidic residues
Compositional bias1034-1052Polar residues
Compositional bias1072-1114Basic and acidic residues

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (4)
  • Sequence status
    Complete

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.

  • Length
    1,114
  • Mass (Da)
    124,045
  • Last updated
    2014-03-19 v4
  • Checksum
    AD8DF5FEAB8CBE32
MEAAVGVPDGGDQGGAGPREDATPMDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQVEISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYPIKYKESSAMCQSLLYELLYEKVFKTDVSKIVMELDTLEVADEDNSEISDSEDDSCKSKTAAAAADVNGFKPLSGNEQLKNNGNSTSLPLSRKVLKSLNPAVYRNVEYEIWLKSKQAQQKRDYSIAAGLQYEVGDKCQVRLDHNGKFLNADVQGIHSENGPVLVEELGKKHTSKNLKAPPPESWNTVSGKKMKKPSTSGQNFHSDVDYRGPKNPSKPIKAPSALPPRLQHPSGVRQHAFSSHSSGSQSQKFSSEHKNLSRTPSQIIRKPDRERVEDFDHTSRESNYFGLSPEERREKQAIEESRLLYEIQNRDEQAFPALSSSSVNQSASQSSNPCVQRKSSHVGDRKGSRRRMDTEERKDKDSIHGHSQLDKRPEPSTLENITDDKYATVSSPSKSKKLECPSPAEQKPAEHVSLSNPAPLLVSPEVHLTPAVPSLPATVPAWPSEPTTFGPTGVPAPIPVLSVTQTLTTGPDSAVSQAHLTPSPVPVSIQAVNQPLMPLPQTLSLYQDPLYPGFPCNEKGDRAIVPPYSLCQTGEDLPKDKNILRFFFNLGVKAYSCPMWAPHSYLYPLHQAYLAACRMYPKVPVPVYPHNPWFQEAPAAQNESDCTCTDAHFPMQTEASVNGQMPQPEIGPPTFSSPLVIPPSQVSESHGQLSYQADLESETPGQLLHADYEESLSGKNMFPQPSFGPNPFLGPVPIAPPFFPHVWYGYPFQGFIENPVMRQNIVLPSDEKGELDLSLENLDLSKDCGSVSTVDEFPEARGEHVHSLPEASVSSKPDEGRTEQSSQTRKADTALASIPPVAEGKAHPPTQILNRERETVPVELEPKRTIQSLKEKTEKVKDPKTAADVVSPGANSVDSRVQRPKEESSEDENEVSNILRSGRSKQFYNQTYGSRKYKSDWGYSGRGGYQHVRSEESWKGQPSRSRDEGYQYHRNVRGRPFRGDRRRSGMGDGHRGQHT

Q01804-5

Q01804-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q01804-4

  • Name
    4
  • Note
    Predicted from a chimeric transcript isolated from HIV-1-infected cells. The premature stop may be due to intron retention.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
D6RI06D6RI06_HUMANOTUD4372
D6RA27D6RA27_HUMANOTUD4139

Sequence caution

The sequence AAH57242.2 differs from that shown. Reason: Miscellaneous discrepancy Sequence of unknown origin in the N-terminal part.
The sequence BAA82998.2 differs from that shown. Reason: Miscellaneous discrepancy Intron retention.
The sequence BAB71229.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Features

Showing features for alternative sequence, compositional bias, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0388301-65in isoform 2, isoform 3 and isoform 4
Alternative sequenceVSP_021671211-1114in isoform 4
Alternative sequenceVSP_053825231in isoform 2
Compositional bias342-357Polar residues
Compositional bias387-417Polar residues
Compositional bias418-449Basic and acidic residues
Compositional bias472-493Polar residues
Compositional bias494-534Basic and acidic residues
Compositional bias536-552Polar residues
Sequence conflict809in Ref. 1; BAB71229
Sequence conflict915in Ref. 9; CAB70748
Compositional bias973-1000Basic and acidic residues
Compositional bias1015-1033Basic and acidic residues
Compositional bias1034-1052Polar residues
Compositional bias1072-1114Basic and acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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