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Q3UCV8 (OTUL_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 59. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Fam105b
Synonyms:Gum
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length352 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4

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). Ref.4

Subunit structure

Interacts with RNF31; the interaction is direct. Interacts with DVL2. Ref.4

Subcellular location

Cytoplasm Ref.4.

Developmental stage

Enriched in a subset of endothelial cells near presumptive tips of vessels and vascular buds (at protein level). Ref.4

Domain

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

Post-translational modification

Ubiquitinated By similarity.

Acetylated By similarity.

Phosphorylated By similarity.

Sequence similarities

Belongs to the peptidase C65 family. Otulin subfamily.

Contains 1 OTU domain.

Sequence caution

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 annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 352352Ubiquitin thioesterase otulin
PRO_0000261638

Regions

Domain118 – 346229OTU
Region95 – 962Linear diubiquitin binding By similarity
Region124 – 1263Linear diubiquitin binding By similarity
Region255 – 2595Linear diubiquitin binding By similarity
Region283 – 2897Linear diubiquitin binding By similarity
Region336 – 3383Linear diubiquitin binding By similarity
Coiled coil49 – 7325 Potential
Motif349 – 3524PDZ-binding

Sites

Active site1261 Ref.4
Active site1291Nucleophile Ref.4
Active site3391 Ref.4
Binding site3141Linear diubiquitin

Experimental info

Mutagenesis961W → 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. Ref.4
Mutagenesis1291C → A or S: Abolishes deubiquitinase activity without affecting interaction with RNF31. Ref.4
Mutagenesis3361D → E in Gum(D366E) mutant; defects in embryonic angiogenesis. Weaker mutant compared to Gum(W96R) mutant. Ref.4
Mutagenesis349 – 3524ETSV → AAAA: Does not affect interaction with RNF31. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q3UCV8 [UniParc].

Last modified October 11, 2005. Version 1.
Checksum: 435B9B3F4BDEEDDA

FASTA35240,320
        10         20         30         40         50         60 
MSRGTMPQPG AWPGASCAET PAREAGAAAR DGGKVTAGAQ PRAATRCPAE HEEDMYRAAD 

        70         80         90        100        110        120 
EIEKEKELLI HERGISEPRL SVAPEMDIMD YCKKEWRGNT QKATCMKKGY EEVSQKFTSI 

       130        140        150        160        170        180 
RRVRGDNYCA LRATLFQAMS QLAELPPWLQ DLELILLPEK LINKYTWIKQ WKLGLKFDGK 

       190        200        210        220        230        240 
SEDLVEKIKE SLALLRKKWV SLAAMKTAEA RQTACDELFT NEEEEYSLYE AVKFLMLNRA 

       250        260        270        280        290        300 
IELYDDKEKG KEVPFFSVLL FARDTSNDPE QLLRNHLNQV GHTGGLEQVE MFLLAYAVRH 

       310        320        330        340        350 
SIRVYRLSKY NTEEFITVYP TDPPKDWPMV TLIAEDDRHY NIPVRVCEET SV 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis."
Rivkin E., Almeida S.M., Ceccarelli D.F., Juang Y.C., Maclean T.A., Srikumar T., Huang H., Dunham W.H., Fukumura R., Xie G., Gondo Y., Raught B., Gingras A.C., Sicheri F., Cordes S.P.
Nature 498:318-324(2013) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001013814.2. NM_001013792.2.
UniGeneMm.309164.

3D structure databases

ProteinModelPortalQ3UCV8.
SMRQ3UCV8. Positions 80-346.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ3UCV8.

Proteomic databases

PaxDbQ3UCV8.
PRIDEQ3UCV8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000059662; ENSMUSP00000057893; ENSMUSG00000046034.
GeneID432940.
KEGGmmu:432940.
UCSCuc007vjr.1. mouse.

Organism-specific databases

CTD90268.
MGIMGI:3577015. Fam105b.

Phylogenomic databases

eggNOGNOG47891.
GeneTreeENSGT00390000009802.
HOGENOMHOG000294085.
HOVERGENHBG104927.
InParanoidQ3UCV8.
OMAKYNTEEF.
OrthoDBEOG76QFHQ.
PhylomeDBQ3UCV8.
TreeFamTF328709.

Gene expression databases

BgeeQ3UCV8.
GenevestigatorQ3UCV8.

Family and domain databases

InterProIPR023235. FAM105.
IPR023237. FAM105B.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PfamPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PRINTSPR02055. PROTEINF105.
PR02057. PROTEINF105B.
ProtoNetSearch...

Other

NextBio408130.
PROQ3UCV8.
SOURCESearch...

Entry information

Entry nameOTUL_MOUSE
AccessionPrimary (citable) accession number: Q3UCV8
Secondary accession number(s): Q3UY59, Q5M8N1, Q8R027
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: October 11, 2005
Last modified: April 16, 2014
This is version 59 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant 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