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 OTUB1

Gene

OTUB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

  • NEDD8-specific protease activity Source: UniProtKB
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • DNA repair Source: UniProtKB-KW
  • immune system process Source: UniProtKB-KW
  • negative regulation of double-strand break repair Source: UniProtKB
  • negative regulation of histone H2A K63-linked ubiquitination Source: UniProtKB
  • protein K48-linked deubiquitination Source: UniProtKB
Complete GO annotation...

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 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:23077. OTUB1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

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.

Polymorphism and mutation databases

BioMutaiOTUB1.
DMDMi44888286.

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

BgeeiQ96FW1.
CleanExiHS_OTUB1.
ExpressionAtlasiQ96FW1. baseline and differential.
GenevisibleiQ96FW1. HS.

Organism-specific databases

HPAiCAB072836.
HPA039176.

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
UBE2D3P610777EBI-1058491,EBI-348268
UBE2D4Q9Y2X83EBI-1058491,EBI-745527
ypkAQ569215EBI-1058491,EBI-8022937From a different organism.
ypkAQ9RI123EBI-1058491,EBI-2849107From a different organism.

Protein-protein interaction databases

BioGridi120751. 70 interactions.
DIPiDIP-41158N.
IntActiQ96FW1. 27 interactions.
MINTiMINT-5001867.
STRINGi9606.ENSP00000402551.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00390000006979.
HOVERGENiHBG053383.
InParanoidiQ96FW1.
KOiK09602.
PhylomeDBiQ96FW1.
TreeFamiTF314145.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR030298. OTUB1.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF16. PTHR12931:SF16. 1 hit.
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. AlignAdd to basket

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

        10         20         30         40         50
MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE
60 70 80 90 100
RLELSVLYKE YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH
110 120 130 140 150
LEALLDDSKE LQRFKAVSAK SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE
160 170 180 190 200
KQTSVADLLA SFNDQSTSDY LVVYLRLLTS GYLQRESKFF EHFIEGGRTV
210 220 230 240 250
KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE GGTTNPHIFP
260 270
EGSEPKVYLL YRPGHYDILY K
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. Curated

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:
EMBLi
GenBanki
DDBJi
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]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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...

Protein-protein interaction databases

BioGridi120751. 70 interactions.
DIPiDIP-41158N.
IntActiQ96FW1. 27 interactions.
MINTiMINT-5001867.
STRINGi9606.ENSP00000402551.

Protein family/group databases

MEROPSiC65.001.

PTM databases

PhosphoSiteiQ96FW1.

Polymorphism and mutation databases

BioMutaiOTUB1.
DMDMi44888286.

Proteomic databases

MaxQBiQ96FW1.
PaxDbiQ96FW1.
PRIDEiQ96FW1.

Protocols and materials databases

DNASUi55611.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi55611.
GeneCardsiGC11P063753.
HGNCiHGNC:23077. OTUB1.
HPAiCAB072836.
HPA039176.
MIMi608337. gene.
neXtProtiNX_Q96FW1.
PharmGKBiPA134988141.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG267426.
GeneTreeiENSGT00390000006979.
HOVERGENiHBG053383.
InParanoidiQ96FW1.
KOiK09602.
PhylomeDBiQ96FW1.
TreeFamiTF314145.

Miscellaneous databases

ChiTaRSiOTUB1. human.
EvolutionaryTraceiQ96FW1.
GeneWikiiOTUB1.
GenomeRNAii55611.
NextBioi60179.
PROiQ96FW1.
SOURCEiSearch...

Gene expression databases

BgeeiQ96FW1.
CleanExiHS_OTUB1.
ExpressionAtlasiQ96FW1. baseline and differential.
GenevisibleiQ96FW1. HS.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR030298. OTUB1.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF16. PTHR12931:SF16. 1 hit.
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFiPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEiPS50802. OTU. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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], CLEAVAGE OF INITIATOR METHIONINE [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. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  17. "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.
  18. 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.
  19. "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: June 24, 2015
This is version 131 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

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.