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Protein

Ubiquitin thioesterase otulin

Gene

Otulin

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates. Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex. Acts as a negative regulator of NF-kappa-B by counteracting activity of the LUBAC complex. Plays a key role in innate immune response: required to restrict linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling.1 Publication

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).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei126 – 12611 Publication
Active sitei129 – 1291Nucleophile1 Publication
Binding sitei314 – 3141Linear diubiquitin
Active sitei339 – 33911 Publication

GO - Molecular functioni

  • cysteine-type peptidase activity Source: UniProtKB
  • ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Angiogenesis, Immunity, Innate immunity, Ubl conjugation pathway, Wnt signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin thioesterase otulin (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme otulin
OTU domain-containing deubiquitinase with linear linkage specificity
Ubiquitin thioesterase Gumby
Gene namesi
Name:Otulin
Synonyms:Fam105b, Gum
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:3577015. Otulin.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi96 – 961W → 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
Mutagenesisi129 – 1291C → A or S: Abolishes deubiquitinase activity without affecting interaction with RNF31. 1 Publication
Mutagenesisi336 – 3361D → E in Gum(D366E) mutant; defects in embryonic angiogenesis. Weaker mutant compared to Gum(W96R) mutant. 1 Publication
Mutagenesisi349 – 3524ETSV → AAAA: Does not affect interaction with RNF31. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 352352Ubiquitin thioesterase otulinPRO_0000261638Add
BLAST

Post-translational modificationi

Ubiquitinated.By similarity
Acetylated.By similarity
Phosphorylated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ3UCV8.
PaxDbiQ3UCV8.
PRIDEiQ3UCV8.

PTM databases

PhosphoSiteiQ3UCV8.

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

BgeeiQ3UCV8.
GenevisibleiQ3UCV8. MM.

Interactioni

Subunit structurei

Interacts with RNF31; the interaction is direct. Interacts with DVL2.1 Publication

Protein-protein interaction databases

BioGridi240910. 1 interaction.
STRINGi10090.ENSMUSP00000057893.

Structurei

3D structure databases

ProteinModelPortaliQ3UCV8.
SMRiQ3UCV8. Positions 80-346.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini118 – 346229OTUAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni95 – 962Linear diubiquitin bindingBy similarity
Regioni124 – 1263Linear diubiquitin bindingBy similarity
Regioni255 – 2595Linear diubiquitin bindingBy similarity
Regioni283 – 2897Linear diubiquitin bindingBy similarity
Regioni336 – 3383Linear diubiquitin bindingBy similarity

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili49 – 7325Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi349 – 3524PDZ-binding

Domaini

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

Sequence similaritiesi

Belongs to the peptidase C65 family. Otulin subfamily.Curated
Contains 1 OTU domain.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiNOG47891.
GeneTreeiENSGT00390000009802.
HOGENOMiHOG000294085.
HOVERGENiHBG104927.
InParanoidiQ3UCV8.
KOiK18343.
OMAiKYNTEEF.
OrthoDBiEOG76QFHQ.
PhylomeDBiQ3UCV8.
TreeFamiTF328709.

Family and domain databases

InterProiIPR023235. FAM105.
IPR023237. FAM105B.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PRINTSiPR02055. PROTEINF105.
PR02057. PROTEINF105B.

Sequencei

Sequence statusi: Complete.

Q3UCV8-1 [UniParc]FASTAAdd 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
GO

Sequence cautioni

The sequence AAH87945.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAE22354.1 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.
CCDSiCCDS49586.1.
RefSeqiNP_001013814.2. NM_001013792.2.
UniGeneiMm.309164.

Genome annotation databases

EnsembliENSMUST00000059662; ENSMUSP00000057893; ENSMUSG00000046034.
GeneIDi432940.
KEGGimmu:432940.
UCSCiuc007vjr.1. mouse.

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.
CCDSiCCDS49586.1.
RefSeqiNP_001013814.2. NM_001013792.2.
UniGeneiMm.309164.

3D structure databases

ProteinModelPortaliQ3UCV8.
SMRiQ3UCV8. Positions 80-346.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi240910. 1 interaction.
STRINGi10090.ENSMUSP00000057893.

PTM databases

PhosphoSiteiQ3UCV8.

Proteomic databases

MaxQBiQ3UCV8.
PaxDbiQ3UCV8.
PRIDEiQ3UCV8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000059662; ENSMUSP00000057893; ENSMUSG00000046034.
GeneIDi432940.
KEGGimmu:432940.
UCSCiuc007vjr.1. mouse.

Organism-specific databases

CTDi90268.
MGIiMGI:3577015. Otulin.

Phylogenomic databases

eggNOGiNOG47891.
GeneTreeiENSGT00390000009802.
HOGENOMiHOG000294085.
HOVERGENiHBG104927.
InParanoidiQ3UCV8.
KOiK18343.
OMAiKYNTEEF.
OrthoDBiEOG76QFHQ.
PhylomeDBiQ3UCV8.
TreeFamiTF328709.

Miscellaneous databases

NextBioi408130.
PROiQ3UCV8.
SOURCEiSearch...

Gene expression databases

BgeeiQ3UCV8.
GenevisibleiQ3UCV8. MM.

Family and domain databases

InterProiIPR023235. FAM105.
IPR023237. FAM105B.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PRINTSiPR02055. PROTEINF105.
PR02057. PROTEINF105B.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Bone marrow and Olfactory bulb.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 106-352.
    Tissue: Mammary gland and Molar.
  4. Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, ACTIVE SITE, INTERACTION WITH RNF31 AND DVL2, MUTAGENESIS OF TRP-96; CYS-129; ASP-336 AND 349-GLU--VAL-352.

Entry informationi

Entry nameiOTUL_MOUSE
AccessioniPrimary (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: June 24, 2015
This is version 67 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.