Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ubiquitin thioesterase otulin

Gene

OTULIN

Organism
Homo sapiens (Human)
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.4 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

Kineticsi

Kcat is 6.3 sec(-1) with linear diubiquitin as substrate.

  1. KM=7.98 µM for linear diubiquitin1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei126 – 1261By similarity
Active sitei129 – 1291Nucleophile
Binding sitei314 – 3141Linear diubiquitin2 Publications
Active sitei339 – 3391

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
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:25118. OTULIN.

Subcellular locationi

Cytoplasm 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. LUBAC complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi91 – 911Y → F: Results in strong reduction of kcat while not affecting KM. 1 Publication
Mutagenesisi96 – 961W → A: Decreased activity toward linear ubiquitin. 2 Publications
Mutagenesisi100 – 1023TQK → AAA: Decreased activity toward linear ubiquitin. 1 Publication
Mutagenesisi129 – 1291C → A: Abolishes deubiquitinase activity. 3 Publications
Mutagenesisi259 – 2591L → E: Decreased affinity for linear diubiquitin. 1 Publication
Mutagenesisi314 – 3141E → R: Decreased affinity for linear diubiquitin. 1 Publication
Mutagenesisi336 – 3361D → A: Stabilizes H-339 in the active conformation, generating a more reactive enzyme. 1 Publication
Mutagenesisi339 – 3391H → A: Impaired deubiquitinase activity. 1 Publication
Mutagenesisi341 – 3411N → A: Abolishes deubiquitinase activity. 1 Publication
Mutagenesisi341 – 3411N → D: Stabilizes H-339 in the active conformation, generating a more reactive enzyme. 1 Publication

Organism-specific databases

PharmGKBiPA142671789.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 352352Ubiquitin thioesterase otulinPRO_0000261637Add
BLAST

Post-translational modificationi

Ubiquitinated.1 Publication
Acetylated.1 Publication
Phosphorylated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ96BN8.
PaxDbiQ96BN8.
PeptideAtlasiQ96BN8.
PRIDEiQ96BN8.

PTM databases

PhosphoSiteiQ96BN8.

Expressioni

Gene expression databases

BgeeiQ96BN8.
CleanExiHS_FAM105B.
ExpressionAtlasiQ96BN8. baseline and differential.
GenevestigatoriQ96BN8.

Organism-specific databases

HPAiHPA051074.

Interactioni

Subunit structurei

Interacts with RNF31; the interaction is direct.2 Publications

Protein-protein interaction databases

BioGridi124684. 15 interactions.
IntActiQ96BN8. 2 interactions.
MINTiMINT-7944191.

Structurei

Secondary structure

1
352
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi55 – 573Combined sources
Helixi59 – 635Combined sources
Helixi88 – 958Combined sources
Helixi101 – 11414Combined sources
Beta strandi118 – 1214Combined sources
Helixi129 – 14012Combined sources
Helixi147 – 1504Combined sources
Helixi153 – 16412Combined sources
Helixi166 – 1705Combined sources
Helixi184 – 20421Combined sources
Helixi208 – 21811Combined sources
Beta strandi220 – 2223Combined sources
Helixi223 – 24826Combined sources
Helixi255 – 2628Combined sources
Beta strandi263 – 2653Combined sources
Helixi269 – 2757Combined sources
Helixi277 – 2793Combined sources
Turni280 – 2823Combined sources
Helixi288 – 29811Combined sources
Beta strandi301 – 3066Combined sources
Helixi307 – 3093Combined sources
Helixi313 – 3153Combined sources
Beta strandi316 – 3227Combined sources
Beta strandi329 – 3368Combined sources
Beta strandi339 – 3446Combined sources
Helixi346 – 3483Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3ZNVX-ray1.30A80-352[»]
3ZNXX-ray1.35A80-352[»]
3ZNZX-ray1.90A80-352[»]
4KSJX-ray1.60A79-352[»]
4KSKX-ray2.40A/B55-352[»]
4KSLX-ray2.83A/B/E/G/I/K/M/O/Q/S/U/W79-352[»]
4OYKX-ray2.00C/D49-67[»]
4P0BX-ray2.70B/D52-61[»]
ProteinModelPortaliQ96BN8.
SMRiQ96BN8. 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 binding
Regioni124 – 1263Linear diubiquitin binding
Regioni255 – 2595Linear diubiquitin binding
Regioni283 – 2897Linear diubiquitin binding
Regioni336 – 3383Linear diubiquitin binding

Coiled coil

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

Domaini

The specificity for linear polyubiquitin is given by the 'Glu-16' residue in ubiquitin chain.1 Publication

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.
InParanoidiQ96BN8.
KOiK18343.
OMAiKYNTEEF.
PhylomeDBiQ96BN8.
TreeFamiTF328709.

Family and domain databases

InterProiIPR023235. FAM105.
IPR023237. FAM105B.
[Graphical view]
PRINTSiPR02055. PROTEINF105.
PR02057. PROTEINF105B.

Sequencei

Sequence statusi: Complete.

Q96BN8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRGTMPQPE AWPGASCAET PAREAAATAR DGGKAAASGQ PRPEMQCPAE
60 70 80 90 100
HEEDMYRAAD EIEKEKELLI HERGASEPRL SVAPEMDIMD YCKKEWRGNT
110 120 130 140 150
QKATCMKMGY EEVSQKFTSI RRVRGDNYCA LRATLFQAMS QAVGLPPWLQ
160 170 180 190 200
DPELMLLPEK LISKYNWIKQ WKLGLKFDGK NEDLVDKIKE SLTLLRKKWA
210 220 230 240 250
GLAEMRTAEA RQIACDELFT NEAEEYSLYE AVKFLMLNRA IELYNDKEKG
260 270 280 290 300
KEVPFFSVLL FARDTSNDPG QLLRNHLNQV GHTGGLEQVE MFLLAYAVRH
310 320 330 340 350
TIQVYRLSKY NTEEFITVYP TDPPKDWPVV TLIAEDDRHY NIPVRVCEET

SL
Length:352
Mass (Da):40,263
Last modified:November 28, 2006 - v3
Checksum:i65071FF7B427C2FA
GO

Sequence cautioni

The sequence AAH07706.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH15392.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC03828.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti211 – 2111R → G in BAC03828 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti155 – 1551M → L.
Corresponds to variant rs11953822 [ dbSNP | Ensembl ].
VAR_053819
Natural varianti227 – 2271S → N.
Corresponds to variant rs9312870 [ dbSNP | Ensembl ].
VAR_029469
Natural varianti311 – 3111N → S.
Corresponds to variant rs9312870 [ dbSNP | Ensembl ].
VAR_053820

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC010491 Genomic DNA. No translation available.
CH471102 Genomic DNA. Translation: EAX08038.1.
CH471102 Genomic DNA. Translation: EAX08039.1.
BC007706 mRNA. Translation: AAH07706.3. Different initiation.
BC015392 mRNA. Translation: AAH15392.2. Different initiation.
AK092203 mRNA. Translation: BAC03828.1. Different initiation.
CCDSiCCDS43302.1.
RefSeqiNP_612357.4. NM_138348.4.
UniGeneiHs.406335.

Genome annotation databases

EnsembliENST00000284274; ENSP00000284274; ENSG00000154124.
GeneIDi90268.
KEGGihsa:90268.
UCSCiuc003jfk.3. human.

Polymorphism databases

DMDMi118572305.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC010491 Genomic DNA. No translation available.
CH471102 Genomic DNA. Translation: EAX08038.1.
CH471102 Genomic DNA. Translation: EAX08039.1.
BC007706 mRNA. Translation: AAH07706.3. Different initiation.
BC015392 mRNA. Translation: AAH15392.2. Different initiation.
AK092203 mRNA. Translation: BAC03828.1. Different initiation.
CCDSiCCDS43302.1.
RefSeqiNP_612357.4. NM_138348.4.
UniGeneiHs.406335.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3ZNVX-ray1.30A80-352[»]
3ZNXX-ray1.35A80-352[»]
3ZNZX-ray1.90A80-352[»]
4KSJX-ray1.60A79-352[»]
4KSKX-ray2.40A/B55-352[»]
4KSLX-ray2.83A/B/E/G/I/K/M/O/Q/S/U/W79-352[»]
4OYKX-ray2.00C/D49-67[»]
4P0BX-ray2.70B/D52-61[»]
ProteinModelPortaliQ96BN8.
SMRiQ96BN8. Positions 80-346.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124684. 15 interactions.
IntActiQ96BN8. 2 interactions.
MINTiMINT-7944191.

PTM databases

PhosphoSiteiQ96BN8.

Polymorphism databases

DMDMi118572305.

Proteomic databases

MaxQBiQ96BN8.
PaxDbiQ96BN8.
PeptideAtlasiQ96BN8.
PRIDEiQ96BN8.

Protocols and materials databases

DNASUi90268.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000284274; ENSP00000284274; ENSG00000154124.
GeneIDi90268.
KEGGihsa:90268.
UCSCiuc003jfk.3. human.

Organism-specific databases

CTDi90268.
GeneCardsiGC05P014667.
HGNCiHGNC:25118. OTULIN.
HPAiHPA051074.
neXtProtiNX_Q96BN8.
PharmGKBiPA142671789.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG47891.
GeneTreeiENSGT00390000009802.
HOGENOMiHOG000294085.
HOVERGENiHBG104927.
InParanoidiQ96BN8.
KOiK18343.
OMAiKYNTEEF.
PhylomeDBiQ96BN8.
TreeFamiTF328709.

Miscellaneous databases

GenomeRNAii90268.
NextBioi76620.
PROiQ96BN8.

Gene expression databases

BgeeiQ96BN8.
CleanExiHS_FAM105B.
ExpressionAtlasiQ96BN8. baseline and differential.
GenevestigatoriQ96BN8.

Family and domain databases

InterProiIPR023235. FAM105.
IPR023237. FAM105B.
[Graphical view]
PRINTSiPR02055. PROTEINF105.
PR02057. PROTEINF105B.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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].
    Tissue: Ovary and Prostate.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 123-298.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. "OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis."
    Mevissen T.E., Hospenthal M.K., Geurink P.P., Elliott P.R., Akutsu M., Arnaudo N., Ekkebus R., Kulathu Y., Wauer T., El Oualid F., Freund S.M., Ovaa H., Komander D.
    Cell 154:169-184(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY.
  7. Cited for: FUNCTION, MUTAGENESIS OF TRP-96 AND CYS-129.
  8. Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF MUTANT ASP-336, X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEX WITH LINEAR DIUBIQUITIN, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, PHOSPHORYLATION, UBIQUITINATION, ACETYLATION, MUTAGENESIS OF TYR-91; TRP-96; 100-THR--LYS-102; CYS-129; LEU-259; GLU-314; ASP-336; HIS-339 AND ASN-341.
  9. Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 79-352 OF MUTANT CYS-129, X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 79-352 OF MUTANT CYS-129 IN COMPLEX WITH LINEAR DIUBIQUITIN, FUNCTION, INTERACTION WITH RNF31 AND DVL2, MUTAGENESIS OF CYS-129.

Entry informationi

Entry nameiOTUL_HUMAN
AccessioniPrimary (citable) accession number: Q96BN8
Secondary accession number(s): D3DTD3, Q8NAS0, Q96IA3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: November 28, 2006
Last modified: February 4, 2015
This is version 81 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. 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.