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Q96FW1

- OTUB1_HUMAN

UniProt

Q96FW1 - OTUB1_HUMAN

Protein

Ubiquitin thioesterase OTUB1

Gene

OTUB1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 2 (01 Mar 2004)
      Previous versions | rss
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    Functioni

    Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin.
    Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain.

    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

    Enzyme regulationi

    By free ubiquitin: binding of free ubiquitin triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N-terminus, promoting binding of the conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei23 – 231Required for proximal ubiquitin-binding
    Active sitei88 – 881
    Active sitei91 – 911Nucleophile
    Binding sitei221 – 2211Free ubiquitin
    Binding sitei235 – 2351Free ubiquitin
    Binding sitei237 – 2371Free ubiquitin
    Binding sitei261 – 2611Free ubiquitin
    Active sitei265 – 2651
    Binding sitei266 – 2661Free ubiquitin

    GO - Molecular functioni

    1. NEDD8-specific protease activity Source: UniProtKB
    2. omega peptidase activity Source: InterPro
    3. protein binding Source: UniProtKB
    4. ubiquitin binding Source: UniProtKB
    5. ubiquitin protein ligase binding Source: UniProtKB
    6. ubiquitin-specific protease activity Source: UniProtKB

    GO - Biological processi

    1. cellular response to DNA damage stimulus Source: UniProtKB
    2. DNA repair Source: UniProtKB-KW
    3. immune system process Source: UniProtKB-KW
    4. negative regulation of double-strand break repair Source: UniProtKB
    5. negative regulation of histone H2A K63-linked ubiquitination Source: UniProtKB
    6. protein K48-linked deubiquitination Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Adaptive immunity, DNA damage, DNA repair, Immunity, Ubl conjugation pathway

    Protein family/group databases

    MEROPSiC65.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin thioesterase OTUB1 (EC:3.4.19.12)
    Alternative name(s):
    Deubiquitinating enzyme OTUB1
    OTU domain-containing ubiquitin aldehyde-binding protein 1
    Otubain-1
    Short name:
    hOTU1
    Ubiquitin-specific-processing protease OTUB1
    Gene namesi
    Name:OTUB1
    Synonyms:OTB1, OTU1
    ORF Names:HSPC263
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:23077. OTUB1.

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. extracellular vesicular exosome Source: UniProt

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi23 – 231C → A: Abolishes only ubiquitin-vinylsulfone adduct formation. 1 Publication
    Mutagenesisi33 – 331Q → R: Impairs inhibition of UBE2N/UBC13. 1 Publication
    Mutagenesisi37 – 371I → T: Impairs inhibition of UBE2N/UBC13. 1 Publication
    Mutagenesisi39 – 391Q → L: Does not affect activity in DNA repair and ability to inhibit UBE2N/UBC13. 1 Publication
    Mutagenesisi87 – 871P → G: Slightly improves ability to cleave 'K63'-linked ubiquitin. 1 Publication
    Mutagenesisi88 – 881D → E: Abolishes hydrolase activity in vitro. Abolishes ability to inhibit RNF168; when associated with S-91 and A-265. 2 Publications
    Mutagenesisi91 – 911C → A: Prevents RNF128 autoubiquitination, and stabilizes RNF128 in vivo. Abolishes both ubiquitin-binding and adduct formation with ubiquitin-vinylsulfone. 7 Publications
    Mutagenesisi91 – 911C → S: Abolishes hydrolase activity in vitro. Does not affect ability to inhibit RNF168. Abolishes ability to inhibit RNF168; when associated with A-88 and A-265. 7 Publications
    Mutagenesisi116 – 1161A → T: Does not affect ability to inhibit UBE2N/UBC13. 1 Publication
    Mutagenesisi134 – 1341T → R: Impairs inhibition of UBE2N/UBC13. 1 Publication
    Mutagenesisi137 – 1371D → G: Impairs inhibition of UBE2N/UBC13. 1 Publication
    Mutagenesisi176 – 1761R → L: No effect on RNF128. 1 Publication
    Mutagenesisi190 – 1901F → S: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13. 1 Publication
    Mutagenesisi212 – 2121C → A: No effect on RNF128. 2 Publications
    Mutagenesisi261 – 2611Y → H: Impairs inhibition of UBE2N/UBC13. 1 Publication
    Mutagenesisi263 – 2631P → L: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13. 1 Publication
    Mutagenesisi265 – 2651H → A: Abolishes ability to inhibit RNF168; when associated with A-88 and S-91. 2 Publications
    Mutagenesisi265 – 2651H → R: Abolishes hydrolase activity in vitro. 2 Publications

    Organism-specific databases

    PharmGKBiPA134988141.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed2 Publications
    Chaini2 – 271270Ubiquitin thioesterase OTUB1PRO_0000221008Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine2 Publications
    Modified residuei16 – 161Phosphoserine1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ96FW1.
    PaxDbiQ96FW1.
    PRIDEiQ96FW1.

    PTM databases

    PhosphoSiteiQ96FW1.

    Expressioni

    Tissue specificityi

    Isoform 1 is ubiquitous. Isoform 2 is expressed only in lymphoid tissues such as tonsils, lymph nodes and spleen, as well as peripheral blood mononuclear cells.2 Publications

    Gene expression databases

    ArrayExpressiQ96FW1.
    BgeeiQ96FW1.
    CleanExiHS_OTUB1.
    GenevestigatoriQ96FW1.

    Organism-specific databases

    HPAiHPA039176.

    Interactioni

    Subunit structurei

    Isoform 1 and isoform 2 interact with RNF128. Isoform 1 forms a ternary complex with RNF128 and USP8. Isoform 1 interacts with the C-terminal UCH catalytic domain of USP8. Isoform 2 does not associate with USP8. Interacts with FUS, ESR1 and GNB2L1/RACK1. Interacts with UBE2N/UBC13.6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    BIRC2Q134903EBI-1058491,EBI-514538
    MDM2Q009875EBI-1058491,EBI-389668
    TP53P046378EBI-1058491,EBI-366083
    UBE2D1P516684EBI-1058491,EBI-743540
    UBE2D2P628375EBI-1058491,EBI-347677
    UBE2D3P610774EBI-1058491,EBI-348268
    ypkAQ569215EBI-1058491,EBI-8022937From a different organism.
    ypkAQ9RI123EBI-1058491,EBI-2849107From a different organism.

    Protein-protein interaction databases

    BioGridi120751. 61 interactions.
    DIPiDIP-41158N.
    IntActiQ96FW1. 26 interactions.
    MINTiMINT-5001867.
    STRINGi9606.ENSP00000301453.

    Structurei

    Secondary structure

    1
    271
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi24 – 4421
    Beta strandi47 – 537
    Helixi54 – 607
    Helixi66 – 7510
    Turni76 – 783
    Beta strandi81 – 833
    Beta strandi87 – 893
    Helixi91 – 10414
    Helixi108 – 12720
    Helixi132 – 15019
    Helixi155 – 1628
    Helixi165 – 18521
    Helixi187 – 1904
    Helixi191 – 1933
    Beta strandi194 – 1974
    Helixi200 – 2078
    Helixi217 – 22711
    Beta strandi231 – 2355
    Beta strandi240 – 2423
    Beta strandi245 – 2506
    Beta strandi256 – 2627
    Beta strandi265 – 2706

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2ZFYX-ray1.69A40-271[»]
    3VONX-ray3.15A/H/O/V/c/j45-271[»]
    4DDGX-ray3.30A/B/C/J/K/L25-271[»]
    4DDIX-ray3.80A/B/C25-271[»]
    4DHZX-ray3.11A1-45[»]
    4I6LX-ray2.49A45-271[»]
    4LDTX-ray1.90A1-45[»]
    ProteinModelPortaliQ96FW1.
    SMRiQ96FW1. Positions 25-271.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ96FW1.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini80 – 271192OTUPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni130 – 1389Ubiquitin-conjugating enzyme E2 binding
    Regioni169 – 1779Ubiquitin-conjugating enzyme E2 binding
    Regioni189 – 1957Free ubiquitin binding
    Regioni206 – 2138Ubiquitin-conjugating enzyme E2 binding
    Regioni214 – 2218Free ubiquitin binding
    Regioni245 – 2517Free ubiquitin binding

    Domaini

    In addition to ubiquitin-binding at the Cys-91 active site, a proximal ubiquitin-binding site is also present at Cys-23 Occupancy of the active site is needed to enable tight binding to the second site. Distinct binding sites for the ubiquitins may allow to discriminate among different isopeptide linkages (i.e. 'Lys-48'-, 'Lys-63'-linked polyubiquitin) in polyubiquitin substrates and achieve linkage-specific deubiquitination.1 Publication

    Sequence similaritiesi

    Belongs to the peptidase C65 family.Curated
    Contains 1 OTU domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG267426.
    HOVERGENiHBG053383.
    InParanoidiQ96FW1.
    KOiK09602.
    PhylomeDBiQ96FW1.
    TreeFamiTF314145.

    Family and domain databases

    InterProiIPR003323. OTU.
    IPR019400. Peptidase_C65_otubain.
    IPR016615. Ubiquitin_thioesterase_Otubain.
    [Graphical view]
    PfamiPF10275. Peptidase_C65. 1 hit.
    [Graphical view]
    PIRSFiPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
    PROSITEiPS50802. OTU. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q96FW1-1) [UniParc]FASTAAdd to Basket

    Also known as: Otubain-1

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE    50
    RLELSVLYKE YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH 100
    LEALLDDSKE LQRFKAVSAK SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE 150
    KQTSVADLLA SFNDQSTSDY LVVYLRLLTS GYLQRESKFF EHFIEGGRTV 200
    KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE GGTTNPHIFP 250
    EGSEPKVYLL YRPGHYDILY K 271
    Length:271
    Mass (Da):31,284
    Last modified:March 1, 2004 - v2
    Checksum:i63188EE1DC5FD66F
    GO
    Isoform 2 (identifier: Q96FW1-2) [UniParc]FASTAAdd to Basket

    Also known as: ARF-1

    The sequence of this isoform differs from the canonical sequence as follows:
         1-112: MAAEEPQQQK...ALLDDSKELQ → MMKPSWLSRT...MLGPPFHPTP

    Note: Lacks the catalytic sites for protease activity.

    Show »
    Length:315
    Mass (Da):35,285
    Checksum:i3B37EB8F1B3B2404
    GO

    Sequence cautioni

    The sequence AAF28941.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti61 – 611Y → C in AAH10368. (PubMed:15489334)Curated
    Sequence conflicti151 – 1511K → R in BAA90956. (PubMed:14702039)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 112112MAAEE…SKELQ → MMKPSWLSRTEFSKRLLCRT LWCQSGWSSRSYTRSMLKMT TSINRRSRTSTKSTRTSARP GLTATVSIGLSDSPTWRHCW MTARSCSGEKGGHWAPRQVG VYLLPGRVGCVSSRVSPSFP GDGLDSGLARRGSAVSALAS GLVEEPMLGPPFHPTP in isoform 2. 1 PublicationVSP_009464Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY177200 mRNA. Translation: AAO27702.1.
    AF161381 mRNA. Translation: AAF28941.1. Different initiation.
    AK000120 mRNA. Translation: BAA90956.1.
    AP000721 Genomic DNA. No translation available.
    BC007519 mRNA. Translation: AAH07519.1.
    BC010368 mRNA. Translation: AAH10368.1.
    BC107701 mRNA. Translation: AAI07702.1.
    CCDSiCCDS8055.1. [Q96FW1-1]
    RefSeqiNP_060140.2. NM_017670.2. [Q96FW1-1]
    UniGeneiHs.473788.

    Genome annotation databases

    EnsembliENST00000428192; ENSP00000402551; ENSG00000167770. [Q96FW1-1]
    ENST00000538426; ENSP00000444357; ENSG00000167770. [Q96FW1-1]
    GeneIDi55611.
    KEGGihsa:55611.
    UCSCiuc001nyf.1. human. [Q96FW1-1]
    uc001nyg.1. human. [Q96FW1-2]

    Polymorphism databases

    DMDMi44888286.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY177200 mRNA. Translation: AAO27702.1 .
    AF161381 mRNA. Translation: AAF28941.1 . Different initiation.
    AK000120 mRNA. Translation: BAA90956.1 .
    AP000721 Genomic DNA. No translation available.
    BC007519 mRNA. Translation: AAH07519.1 .
    BC010368 mRNA. Translation: AAH10368.1 .
    BC107701 mRNA. Translation: AAI07702.1 .
    CCDSi CCDS8055.1. [Q96FW1-1 ]
    RefSeqi NP_060140.2. NM_017670.2. [Q96FW1-1 ]
    UniGenei Hs.473788.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2ZFY X-ray 1.69 A 40-271 [» ]
    3VON X-ray 3.15 A/H/O/V/c/j 45-271 [» ]
    4DDG X-ray 3.30 A/B/C/J/K/L 25-271 [» ]
    4DDI X-ray 3.80 A/B/C 25-271 [» ]
    4DHZ X-ray 3.11 A 1-45 [» ]
    4I6L X-ray 2.49 A 45-271 [» ]
    4LDT X-ray 1.90 A 1-45 [» ]
    ProteinModelPortali Q96FW1.
    SMRi Q96FW1. Positions 25-271.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 120751. 61 interactions.
    DIPi DIP-41158N.
    IntActi Q96FW1. 26 interactions.
    MINTi MINT-5001867.
    STRINGi 9606.ENSP00000301453.

    Protein family/group databases

    MEROPSi C65.001.

    PTM databases

    PhosphoSitei Q96FW1.

    Polymorphism databases

    DMDMi 44888286.

    Proteomic databases

    MaxQBi Q96FW1.
    PaxDbi Q96FW1.
    PRIDEi Q96FW1.

    Protocols and materials databases

    DNASUi 55611.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000428192 ; ENSP00000402551 ; ENSG00000167770 . [Q96FW1-1 ]
    ENST00000538426 ; ENSP00000444357 ; ENSG00000167770 . [Q96FW1-1 ]
    GeneIDi 55611.
    KEGGi hsa:55611.
    UCSCi uc001nyf.1. human. [Q96FW1-1 ]
    uc001nyg.1. human. [Q96FW1-2 ]

    Organism-specific databases

    CTDi 55611.
    GeneCardsi GC11P063753.
    HGNCi HGNC:23077. OTUB1.
    HPAi HPA039176.
    MIMi 608337. gene.
    neXtProti NX_Q96FW1.
    PharmGKBi PA134988141.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG267426.
    HOVERGENi HBG053383.
    InParanoidi Q96FW1.
    KOi K09602.
    PhylomeDBi Q96FW1.
    TreeFami TF314145.

    Miscellaneous databases

    ChiTaRSi OTUB1. human.
    EvolutionaryTracei Q96FW1.
    GeneWikii OTUB1.
    GenomeRNAii 55611.
    NextBioi 60179.
    PROi Q96FW1.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96FW1.
    Bgeei Q96FW1.
    CleanExi HS_OTUB1.
    Genevestigatori Q96FW1.

    Family and domain databases

    InterProi IPR003323. OTU.
    IPR019400. Peptidase_C65_otubain.
    IPR016615. Ubiquitin_thioesterase_Otubain.
    [Graphical view ]
    Pfami PF10275. Peptidase_C65. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
    PROSITEi PS50802. OTU. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Otubains: a new family of cysteine proteases in the ubiquitin pathway."
      Balakirev M.Y., Tcherniuk S.O., Jaquinod M., Chroboczek J.
      EMBO Rep. 4:517-522(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-88; CYS-91 AND HIS-265.
      Tissue: Cervix carcinoma.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING, FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH RNF128 AND USP8, MUTAGENESIS OF CYS-91; ARG-176 AND CYS-212.
    3. "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells."
      Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X.
      , Gu J., Chen S.-J., Chen Z.
      Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Umbilical cord blood.
    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] (ISOFORM 1).
      Tissue: Colon.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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] (ISOFORM 1).
      Tissue: Colon and Skin.
    7. "Chemistry-based functional proteomics reveals novel members of the deubiquitinating enzyme family."
      Borodovsky A., Ovaa H., Kolli N., Gan-Erdene T., Wilkinson K.D., Ploegh H.L., Kessler B.M.
      Chem. Biol. 9:1149-1159(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION.
    8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    9. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    10. "OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity."
      Stanisic V., Malovannaya A., Qin J., Lonard D.M., O'Malley B.W.
      J. Biol. Chem. 284:16135-16145(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ESR1, MUTAGENESIS OF CYS-91.
    11. "Evidence for bidentate substrate binding as the basis for the K48 linkage specificity of otubain 1."
      Wang T., Yin L., Cooper E.M., Lai M.-Y., Dickey S., Pickart C.M., Fushman D., Wilkinson K.D., Cohen R.E., Wolberger C.
      J. Mol. Biol. 386:1011-1023(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, UBIQUITIN-BINDING, DOMAIN, MUTAGENESIS OF CYS-23; CYS-91 AND CYS-212.
    12. Cited for: FUNCTION IN INHIBITION OF RNF168, INTERACTION WITH UBE2N/UBC13, MUTAGENESIS OF ASP-88; CYS-91 AND HIS-265.
    13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    14. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    15. "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.
    16. "Structural basis and specificity of human otubain 1-mediated deubiquitination."
      Edelmann M.J., Iphoefer A., Akutsu M., Altun M., di Gleria K., Kramer H.B., Fiebiger E., Dhe-Paganon S., Kessler B.M.
      Biochem. J. 418:379-390(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS) OF 40-271, FUNCTION, INTERACTION WITH FUS AND GNB2L1, MUTAGENESIS OF PRO-87 AND CYS-91.
    17. Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 25-271 IN COMPLEX WITH UBE2V2 AND UBE2N, FREE UBIQUITIN-BINDING, ENZYME REGULATION, MUTAGENESIS OF GLN-33; ILE-37; GLN-39; CYS-91; ALA-116; THR-134; ASP-137; PHE-190; TYR-261 AND PRO-263.
    18. "The mechanism of OTUB1-mediated inhibition of ubiquitination."
      Wiener R., Zhang X., Wang T., Wolberger C.
      Nature 483:618-622(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.11 ANGSTROMS) OF 1-45 IN COMPLEX WITH UBE2N AND UBIQUITIN, ENZYME REGULATION, FREE UBIQUITIN-BINDING.

    Entry informationi

    Entry nameiOTUB1_HUMAN
    AccessioniPrimary (citable) accession number: Q96FW1
    Secondary accession number(s): Q32Q78
    , Q96II3, Q9NXQ4, Q9P0B8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 1, 2004
    Last sequence update: March 1, 2004
    Last modified: October 1, 2014
    This is version 123 of the entry and version 2 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

    Miscellaneous

    In the structure described by PubMed:18954305, the His-265 active site of the catalytic triad is located too far to interact directly with the active site Cys-91. A possible explanation is that OTUB1 is in inactive conformation in absence of ubiquitin and a conformation change may move His-265 in the proximity of Cys-91 in presence of ubiquitin substrate.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. Peptidase families
      Classification of peptidase families and list of entries
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3