UniProtKB - Q3UCV8 (OTUL_MOUSE)

BLAST

>sp|Q3UCV8|OTUL_MOUSE Ubiquitin thioesterase otulin OS=Mus musculus OX=10090 GN=Otulin PE=1 SV=1
MSRGTMPQPGAWPGASCAETPAREAGAAARDGGKVTAGAQPRAATRCPAEHEEDMYRAAD
EIEKEKELLIHERGISEPRLSVAPEMDIMDYCKKEWRGNTQKATCMKKGYEEVSQKFTSI
RRVRGDNYCALRATLFQAMSQLAELPPWLQDLELILLPEKLINKYTWIKQWKLGLKFDGK
SEDLVEKIKESLALLRKKWVSLAAMKTAEARQTACDELFTNEEEEYSLYEAVKFLMLNRA
IELYDDKEKGKEVPFFSVLLFARDTSNDPEQLLRNHLNQVGHTGGLEQVEMFLLAYAVRH
SIRVYRLSKYNTEEFITVYPTDPPKDWPMVTLIAEDDRHYNIPVRVCEETSV

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History
Entry version 90 (07 Nov 2018)
Sequence version 1 (11 Oct 2005)
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Protein

Ubiquitin thioesterase otulin

Gene

Otulin

Organism

Mus musculus (Mouse)

Status

Reviewed-Annotation score: -Experimental evidence at protein levelⁱ

Functionⁱ

Deubiquitinase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response (PubMed:23708998, PubMed:27523608, PubMed:29950720). Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex (PubMed:23708998). Acts as a negative regulator of NF-kappa-B by regulating the activity of the LUBAC complex (By similarity). OTULIN function is mainly restricted to homeostasis of the LUBAC complex: acts by removing 'Met-1'-linked autoubiquitination of the LUBAC complex, thereby preventing inactivation of the LUBAC complex (PubMed:29950720). Acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis (PubMed:27523608, PubMed:29950720). In myeloid cell, required to prevent unwarranted secretion of cytokines leading to inflammation and autoimmunity by restricting linear polyubiquitin formation (PubMed:27523608). Plays a role in innate immune response by restricting linear polyubiquitin formation on LUBAC complex in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling (By similarity).By similarity3 Publications

Catalytic activityⁱ

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).2 Publications

Sites

Feature key	Position(s)	DescriptionActions	Length
Active siteⁱ	126	1 Publication	1
Active siteⁱ	129	Nucleophile1 Publication	1
Binding siteⁱ	314	Linear diubiquitin	1
Active siteⁱ	339	1 Publication	1

GO - Molecular functionⁱ

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

innate immune response Source: UniProtKB
negative regulation of inflammatory response
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 27523608
- 29950720
negative regulation of NF-kappaB transcription factor activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 27523608
nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
protein linear deubiquitination
Source: UniProtKB
Inferred from direct assayⁱ
regulation of canonical Wnt signaling pathway
Source: UniProtKB
Inferred from direct assayⁱ
- 23708998
regulation of tumor necrosis factor-mediated signaling pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 27523608
- 29950720
sprouting angiogenesis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23708998
Wnt signaling pathway Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Hydrolase, Protease, Thiol protease
Biological process	Angiogenesis, Immunity, Innate immunity, Ubl conjugation pathway, Wnt signaling pathway

Enzyme and pathway databases

Reactomeⁱ	R-MMU-5357905 Regulation of TNFR1 signaling R-MMU-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes

Reactomeⁱ

R-MMU-5357905 Regulation of TNFR1 signaling
R-MMU-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Ubiquitin thioesterase otulinCurated (EC:3.4.19.122 Publications) Alternative name(s): Deubiquitinating enzyme otulinBy similarity OTU domain-containing deubiquitinase with linear linkage specificityBy similarity Ubiquitin thioesterase Gumby1 Publication
Gene namesⁱ	Name:OtulinImported Synonyms:Fam105bImported, Gum1 Publication
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 15

Organism-specific databases

MGIⁱ	MGI:3577015 Otulin

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Disruption phenotypeⁱ

Embryonic lethality (PubMed:23708998, PubMed:27523608). Specific deletion in immune cells leads to acute systemic inflammation characterized by rapid weight loss, increased levels of pro-inflammatory cytokines in serum, neutrophilia with all the hallmarks of emergency granulopoiesis (PubMed:27523608). Specific deletion in T- or B-cells generates healthy mice with no overt inflammatory phenotypes (PubMed:27523608). In contrast, specific deletion in myeloid cells results in a strong inflammatory phenotype, characterized by chronic inflammation and autoimmunity, caused by sterile autoactivation of inflammatory pathways (PubMed:27523608).2 Publications

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	96	W → R in Gum(W96R) mutant; defects in embryonic angiogenesis. Embryos appear normal before E11.5 but die between E12.5-E14, probably due to defects in organization of branching vascular networks in the head and trunk. 1 Publication	1
Mutagenesisⁱ	129	C → A or S: Abolishes deubiquitinase activity without affecting interaction with RNF31. Lethality at midgestation in knockin mice caused by inactivation of the LUBAC complex, leading to cell death mediated by TNFR1 and RIPK1. 2 Publications	1
Mutagenesisⁱ	336	D → E in Gum(D366E) mutant; defects in embryonic angiogenesis. Weaker mutant compared to Gum(W96R) mutant. 1 Publication	1
Mutagenesisⁱ	349 – 352	ETSV → AAAA: Does not affect interaction with RNF31. 1 Publication	4

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000261638	1 – 352	Ubiquitin thioesterase otulinAdd BLAST		352

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	56	PhosphotyrosineBy similarity		1

Post-translational modificationⁱ

Ubiquitinated.By similarity

Acetylated.By similarity

Phosphorylated. Phosphorylation at Tyr-56 prevents interaction with RNF31; dephosphorylation promotes interaction with RNF31 and the LUBAC complex.By similarity

Keywords - PTMⁱ

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDⁱ	Q3UCV8
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q3UCV8
PaxDbⁱ	Q3UCV8
PeptideAtlas More...PeptideAtlasⁱ	Q3UCV8
PRIDEⁱ	Q3UCV8

PTM databases

iPTMnetⁱ	Q3UCV8
PhosphoSitePlusⁱ	Q3UCV8

Expressionⁱ

Developmental stageⁱ

Enriched in a subset of endothelial cells near presumptive tips of vessels and vascular buds (at protein level).1 Publication

Gene expression databases

Bgeeⁱ	ENSMUSG00000046034 Expressed in 234 organ(s), highest expression level in embryo
Genevisibleⁱ	Q3UCV8 MM

Interactionⁱ

Subunit structureⁱ

Protein-protein interaction databases

BioGridⁱ	240910, 3 interactors
STRINGⁱ	10090.ENSMUSP00000057893

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q3UCV8
SMRⁱ	Q3UCV8
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	118 – 346	OTUAdd BLAST		229

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	95 – 96	Linear diubiquitin bindingBy similarity	2
Regionⁱ	124 – 126	Linear diubiquitin bindingBy similarity	3
Regionⁱ	255 – 259	Linear diubiquitin bindingBy similarity	5
Regionⁱ	283 – 289	Linear diubiquitin bindingBy similarity	7
Regionⁱ	336 – 338	Linear diubiquitin bindingBy similarity	3

Coiled coil

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Coiled coilⁱ	49 – 73	Sequence analysisAdd BLAST		25

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	52 – 57	PIM motifBy similarity		6
Motifⁱ	349 – 352	PDZ-binding		4

Domainⁱ

The specificity for linear polyubiquitin is given by the 'Glu-16' residue in ubiquitin chain.By similarity

The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31. Does not interact with other PUB domain-containing proteins. Phosphorylation at Tyr-56 prevents interaction with RNF31.By similarity

Sequence similaritiesⁱ

Belongs to the peptidase C65 family. Otulin subfamily.Curated

Keywords - Domainⁱ

Coiled coil

Phylogenomic databases

eggNOGⁱ	ENOG410IE61 Eukaryota ENOG4111KB3 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000009802
HOGENOMⁱ	HOG000294085
HOVERGENⁱ	HBG104927
InParanoidⁱ	Q3UCV8
KEGG Orthology (KO) More...KOⁱ	K18343
OMAⁱ	PRDWPVV
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0BXG
PhylomeDBⁱ	Q3UCV8
TreeFamⁱ	TF328709

Family and domain databases

InterProⁱ	View protein in InterPro IPR023235 FAM105 IPR023237 Otulin
PANTHERⁱ	PTHR33662 PTHR33662, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF16218 Peptidase_C101, 1 hit
PRINTSⁱ	PR02055 PROTEINF105 PR02057 PROTEINF105B

Sequence (1+)ⁱ

Sequence statusⁱ: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show all Align All

Q3UCV8-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MSRGTMPQPG AWPGASCAET PAREAGAAAR DGGKVTAGAQ PRAATRCPAE 
        60         70         80         90        100
HEEDMYRAAD EIEKEKELLI HERGISEPRL SVAPEMDIMD YCKKEWRGNT 
       110        120        130        140        150
QKATCMKKGY EEVSQKFTSI RRVRGDNYCA LRATLFQAMS QLAELPPWLQ 
       160        170        180        190        200
DLELILLPEK LINKYTWIKQ WKLGLKFDGK SEDLVEKIKE SLALLRKKWV 
       210        220        230        240        250
SLAAMKTAEA RQTACDELFT NEEEEYSLYE AVKFLMLNRA IELYDDKEKG 
       260        270        280        290        300
KEVPFFSVLL FARDTSNDPE QLLRNHLNQV GHTGGLEQVE MFLLAYAVRH 
       310        320        330        340        350
SIRVYRLSKY NTEEFITVYP TDPPKDWPMV TLIAEDDRHY NIPVRVCEET 

SV

Length:352

Mass (Da):40,320

Last modified:October 11, 2005 - v1

Checksum:ⁱ435B9B3F4BDEEDDA

Computationally mapped potential isoform sequencesⁱ

There are 2 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

A0A2I3BQB7	A0A2I3BQB7_MOUSE	Ubiquitin thioesterase otulin Ubiquitin thioesterase otulin	Otulin	58	Annotation score:
A0A2I3BRS5	A0A2I3BRS5_MOUSE	Ubiquitin thioesterase otulin Ubiquitin thioesterase otulin	Otulin	154	Annotation score:

Sequence cautionⁱ

The sequence AAH87945 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

The sequence BAE22354 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AK134955 mRNA Translation: BAE22354.1 Different initiation. AK150371 mRNA Translation: BAE29504.1 GL456173 Genomic DNA No translation available. BC028541 mRNA Translation: AAH28541.1 BC087945 mRNA Translation: AAH87945.1 Different initiation.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS49586.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001013814.2, NM_001013792.2
UniGeneⁱ	Mm.309164

Genome annotation databases

Ensemblⁱ	ENSMUST00000059662; ENSMUSP00000057893; ENSMUSG00000046034
GeneIDⁱ	432940
KEGGⁱ	mmu:432940
UCSC genome browser More...UCSCⁱ	uc007vjr.1 mouse

Protein	Similar proteins		Species	Score	Length	Source
Q3UCV8	Ubiquitin thioesterase otulin	)	HUMAN		352	UniRef90_Q96BN8
Uncharacterized protein		CERAT		368
Uncharacterized protein		MACNE		368
ubiquitin thioesterase otulin isoform X1		NEOSC		361
ubiquitin thioesterase otulin		LEPWE		298
+85

Protein	Similar proteins		Species	Score	Length	Source
Q3UCV8	Ubiquitin thioesterase otulin	)	HUMAN		352	UniRef50_Q96BN8
Uncharacterized protein		CERAT		368
Uncharacterized protein		MACNE		368
ubiquitin thioesterase otulin isoform X1		NEOSC		361
ubiquitin thioesterase otulin		LEPWE		298
+189

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AK134955 mRNA Translation: BAE22354.1 Different initiation. AK150371 mRNA Translation: BAE29504.1 GL456173 Genomic DNA No translation available. BC028541 mRNA Translation: AAH28541.1 BC087945 mRNA Translation: AAH87945.1 Different initiation.
CCDSⁱ	CCDS49586.1
RefSeqⁱ	NP_001013814.2, NM_001013792.2
UniGeneⁱ	Mm.309164

3D structure databases

ProteinModelPortalⁱ	Q3UCV8
SMRⁱ	Q3UCV8
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	240910, 3 interactors
STRINGⁱ	10090.ENSMUSP00000057893

PTM databases

iPTMnetⁱ	Q3UCV8
PhosphoSitePlusⁱ	Q3UCV8

Proteomic databases

EPDⁱ	Q3UCV8
MaxQBⁱ	Q3UCV8
PaxDbⁱ	Q3UCV8
PeptideAtlasⁱ	Q3UCV8
PRIDEⁱ	Q3UCV8

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000059662; ENSMUSP00000057893; ENSMUSG00000046034
GeneIDⁱ	432940
KEGGⁱ	mmu:432940
UCSCⁱ	uc007vjr.1 mouse

Organism-specific databases

CTDⁱ	90268
MGIⁱ	MGI:3577015 Otulin

Phylogenomic databases

eggNOGⁱ	ENOG410IE61 Eukaryota ENOG4111KB3 LUCA
GeneTreeⁱ	ENSGT00390000009802
HOGENOMⁱ	HOG000294085
HOVERGENⁱ	HBG104927
InParanoidⁱ	Q3UCV8
KOⁱ	K18343
OMAⁱ	PRDWPVV
OrthoDBⁱ	EOG091G0BXG
PhylomeDBⁱ	Q3UCV8
TreeFamⁱ	TF328709

Enzyme and pathway databases

Reactomeⁱ	R-MMU-5357905 Regulation of TNFR1 signaling R-MMU-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes

Reactomeⁱ

R-MMU-5357905 Regulation of TNFR1 signaling
R-MMU-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes

Miscellaneous databases

ChiTaRSⁱ	Otulin mouse
Protein Ontology More...PROⁱ	PR:Q3UCV8
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000046034 Expressed in 234 organ(s), highest expression level in embryo
Genevisibleⁱ	Q3UCV8 MM

Family and domain databases

InterProⁱ	View protein in InterPro IPR023235 FAM105 IPR023237 Otulin
PANTHERⁱ	PTHR33662 PTHR33662, 1 hit
Pfamⁱ	View protein in Pfam PF16218 Peptidase_C101, 1 hit
PRINTSⁱ	PR02055 PROTEINF105 PR02057 PROTEINF105B
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	OTUL_MOUSE
Accessionⁱ	Q3UCV8Primary (citable) accession number: Q3UCV8 Secondary accession number(s): Q3UY59, Q5M8N1, Q8R027
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
	Last sequence update:	October 11, 2005
	Last modified:	November 7, 2018
	This is version 90 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Peptidase families
Classification of peptidase families and list of entries
MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q3UCV8 (OTUL_MOUSE)

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Ubiquitin thioesterase otulin

Otulin

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Other locations

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Coiled coil

Motif

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Sequence cautionⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ