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Q3UCV8

- OTUL_MOUSE

UniProt

Q3UCV8 - OTUL_MOUSE

Protein

Ubiquitin thioesterase otulin

Gene

Otulin

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 64 (01 Oct 2014)
      Sequence version 1 (11 Oct 2005)
      Previous versions | rss
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    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

    1. cysteine-type peptidase activity Source: UniProtKB
    2. ubiquitin-specific protease activity Source: UniProtKB

    GO - Biological processi

    1. canonical Wnt signaling pathway Source: UniProtKB
    2. innate immune response Source: UniProtKB
    3. negative regulation of inflammatory response Source: UniProtKB
    4. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
    5. nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
    6. protein linear deubiquitination Source: UniProtKB
    7. sprouting angiogenesis Source: UniProtKB

    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: Chromosome 15

    Organism-specific databases

    MGIiMGI:3577015. Otulin.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB

    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.

    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.
    GenevestigatoriQ3UCV8.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    BioGridi240910. 1 interaction.

    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

    MSRGTMPQPG AWPGASCAET PAREAGAAAR DGGKVTAGAQ PRAATRCPAE    50
    HEEDMYRAAD EIEKEKELLI HERGISEPRL SVAPEMDIMD YCKKEWRGNT 100
    QKATCMKKGY EEVSQKFTSI RRVRGDNYCA LRATLFQAMS QLAELPPWLQ 150
    DLELILLPEK LINKYTWIKQ WKLGLKFDGK SEDLVEKIKE SLALLRKKWV 200
    SLAAMKTAEA RQTACDELFT NEEEEYSLYE AVKFLMLNRA IELYDDKEKG 250
    KEVPFFSVLL FARDTSNDPE QLLRNHLNQV GHTGGLEQVE MFLLAYAVRH 300
    SIRVYRLSKY NTEEFITVYP TDPPKDWPMV TLIAEDDRHY NIPVRVCEET 350
    SV 352
    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.
    The sequence BAE22354.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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. Positions 80-346.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 240910. 1 interaction.

    PTM databases

    PhosphoSitei Q3UCV8.

    Proteomic databases

    MaxQBi Q3UCV8.
    PaxDbi Q3UCV8.
    PRIDEi Q3UCV8.

    Protocols and materials databases

    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 NOG47891.
    GeneTreei ENSGT00390000009802.
    HOGENOMi HOG000294085.
    HOVERGENi HBG104927.
    InParanoidi Q3UCV8.
    KOi K18343.
    OMAi KYNTEEF.
    OrthoDBi EOG76QFHQ.
    PhylomeDBi Q3UCV8.
    TreeFami TF328709.

    Miscellaneous databases

    NextBioi 408130.
    PROi Q3UCV8.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q3UCV8.
    Genevestigatori Q3UCV8.

    Family and domain databases

    InterProi IPR023235. FAM105.
    IPR023237. FAM105B.
    IPR019400. Peptidase_C65_otubain.
    [Graphical view ]
    Pfami PF10275. Peptidase_C65. 1 hit.
    [Graphical view ]
    PRINTSi PR02055. PROTEINF105.
    PR02057. PROTEINF105B.
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 64 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