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Reviewed, UniProtKB/Swiss-Prot Q96FW1 (OTUB1_HUMAN)

Last modified January 19, 2010. Version 79. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Ubiquitin thioesterase OTUB1
    EC=3.1.2.-
Alternative name(s):
    Otubain-1
      Short name=hOTU1
    OTU domain-containing ubiquitin aldehyde-binding protein 1
    Ubiquitin-specific-processing protease OTUB1
    Deubiquitinating enzyme OTUB1
Gene names
Name: OTUB1
Synonyms: OTB1, OTU1
ORF Names: HSPC263
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length271 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Hydrolase that can remove 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 nuch lower preference compared to 'Lys-48'-linked ubiquitin. Ref.1 Ref.2 Ref.7 Ref.11 Ref.12 Ref.14

Subunit structure

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. Ref.2 Ref.11 Ref.14

Subcellular location

Cytoplasm By similarity.

Tissue specificity

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. Ref.1 Ref.2

Domain

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. Ref.12

Miscellaneous

In the structure described by Ref.14, 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.w.

Sequence similarities

Belongs to the peptidase C65 family.

Contains 1 OTU domain.

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96FW1-1)

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.
Isoform 2 (identifier: Q96FW1-2)

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.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 271270Ubiquitin thioesterase OTUB1
PRO_0000221008

Regions

Domain80 – 271192OTU

Sites

Active site881
Active site911
Active site2651
Site231Required for proximal ubiquitin-binding

Amino acid modifications

Modified residue21N-acetylalanine Ref.10
Modified residue161Phosphoserine Ref.8
Modified residue1881N6-acetyllysine Ref.13

Natural variations

Alternative sequence1 – 112112MAAEE…SKELQ → MMKPSWLSRTEFSKRLLCRT LWCQSGWSSRSYTRSMLKMT TSINRRSRTSTKSTRTSARP GLTATVSIGLSDSPTWRHCW MTARSCSGEKGGHWAPRQVG VYLLPGRVGCVSSRVSPSFP GDGLDSGLARRGSAVSALAS GLVEEPMLGPPFHPTP in isoform 2.
VSP_009464

Experimental info

Mutagenesis231C → A: Abolishes only ubiquitin-vinylsulfone adduct formation. Ref.12
Mutagenesis871P → G: Slightly improves ability to cleave 'K63'-linked ubiquitin. Ref.14
Mutagenesis881D → E: Abolishes hydrolase activity in vitro. Ref.1
Mutagenesis911C → A: Prevents RNF128 autoubiquitination, and stabilizes RNF128 in vivo. Abolishes both ubiquitin-binding and adduct formation with ubiquitin-vinylsulfone. Ref.1 Ref.2 Ref.11 Ref.12 Ref.14
Mutagenesis911C → S: Abolishes hydrolase activity in vitro. Ref.1 Ref.2 Ref.11 Ref.12 Ref.14
Mutagenesis1761R → L: No effect on RNF128. Ref.2
Mutagenesis2121C → A: No effect on RNF128. Ref.2 Ref.12
Mutagenesis2651H → R: Abolishes hydrolase activity in vitro. Ref.1
Sequence conflict611Y → C in AAH10368. Ref.6
Sequence conflict1511K → R in BAA90956. Ref.4

Secondary structure

1 ................................. 271
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Otubain-1) [UniParc].

Last modified March 1, 2004. Version 2.
Checksum: 63188EE1DC5FD66F

FASTA27131,284
        10         20         30         40         50         60 
MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE RLELSVLYKE 

        70         80         90        100        110        120 
YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH LEALLDDSKE LQRFKAVSAK 

       130        140        150        160        170        180 
SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE KQTSVADLLA SFNDQSTSDY LVVYLRLLTS 

       190        200        210        220        230        240 
GYLQRESKFF EHFIEGGRTV KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE 

       250        260        270 
GGTTNPHIFP EGSEPKVYLL YRPGHYDILY K

« Hide

Isoform 2 (ARF-1).

Checksum: 3B37EB8F1B3B2404
Show »

FASTA31535,285

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References

« Hide 'large scale' references
[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: 12704427] [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]"Two isoforms of otubain 1 regulate T cell anergy via GRAIL."
Soares L., Seroogy C., Skrenta H., Anandasabapathy N., Lovelace P., Chung C.D., Engleman E., Fathman C.G.
Nat. Immunol. 5:45-54(2004) [PubMed: 14661020] [Abstract]
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. expand/collapse author list , Gu J., Chen S.-J., Chen Z.
Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [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. expand/collapse author list , 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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon.
[5]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed: 16554811] [Abstract]
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: 15489334] [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: 12401499] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, MASS SPECTROMETRY.
[9]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]"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: 19413330] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY.
[11]"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: 19383985] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ESR1, MUTAGENESIS OF CYS-91.
[12]"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: 19211026] [Abstract]
Cited for: FUNCTION, UBIQUITIN-BINDING, DOMAIN, MUTAGENESIS OF CYS-23; CYS-91 AND CYS-212.
[13]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-188, MASS SPECTROMETRY.
[14]"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: 18954305] [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.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00409750.
IPI00939174.
RefSeqNP_060140.2.
UniGeneHs.473788

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZFYX-ray1.69A40-271[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ96FW1. 13 interactions.
STRINGQ96FW1.

Protein family/group databases

MEROPSC65.001.

PTM databases

PhosphoSiteQ96FW1.

Proteomic databases

PRIDEQ96FW1.

Genome annotation databases

EnsemblENST00000301453; ENSP00000301453; ENSG00000167770; Homo sapiens. [Genome view]
ENST00000422031; ENSP00000416973; ENSG00000167770; Homo sapiens. [Genome view]
GeneID55611.
KEGGhsa:55611.
UCSCuc001nyf.1. human.
uc001nyg.1. human.

Organism-specific databases

CTD55611.
GeneCardsGC11P063510.
H-InvDBHIX0009749.
HGNCHGNC:23077. OTUB1.
MIM608337. gene.
PharmGKBPA134988141.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG17343.
HOVERGENQ96FW1.
InParanoidQ96FW1.
OrthoDBEOG9DJNFZ.
PhylomeDBQ96FW1.

Gene expression databases

ArrayExpressQ96FW1.
BgeeQ96FW1.
CleanExHS_OTUB1.
GenevestigatorQ96FW1.
GermOnlineENSG00000167770. Homo sapiens.

Family and domain databases

InterProIPR003323. OTU.
IPR019400. Peptidase_C65_otubain.
IPR016615. Ubiquitin_thioesterase_Otubain.
[Graphical view]
PfamPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEPS50802. OTU. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio60179.
SOURCESearch...

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Entry information

Entry nameOTUB1_HUMAN
AccessionPrimary (citable) accession number: Q96FW1
Secondary accession number(s): Q32Q78 expand/collapse secondary AC list , Q96II3, Q9NXQ4, Q9P0B8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: January 19, 2010
This is version 79 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Relevant documents

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents