Q96FW1 (OTUB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	OTUB1
Synonyms:	OTB1, OTU1
ORF Names:	HSPC263

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	271 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.2 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13 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. Ref.1 Ref.2 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13
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).
Enzyme regulation	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. Ref.14 Ref.15
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. Interacts with UBE2N/UBC13. Ref.2 Ref.9 Ref.11 Ref.13
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.10
Miscellaneous	In the structure described by Ref.13, 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.
Sequence similarities	Belongs to the peptidase C65 family. Contains 1 OTU domain.
Sequence caution	The sequence AAF28941.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Adaptive immunity DNA damage DNA repair Immunity Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of double-strand break repair Inferred from mutant phenotype Ref.11. Source: UniProtKB negative regulation of histone H2A K63-linked ubiquitination Inferred from direct assay Ref.11. Source: UniProtKB protein K48-linked deubiquitination Inferred from direct assay Ref.13Ref.10. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW response to DNA damage stimulus Inferred from direct assay Ref.11. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	NEDD8-specific protease activity Inferred from direct assay Ref.13. Source: UniProtKB omega peptidase activity Inferred from electronic annotation. Source: InterPro ubiquitin binding Inferred from direct assay Ref.10. Source: UniProtKB ubiquitin-specific protease activity Inferred from direct assay Ref.13Ref.10. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
UBE2D2	P62837	2	EBI-1058491,EBI-347677

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 271

271

Ubiquitin thioesterase OTUB1

PRO_0000221008

Regions

Domain

80 – 271

192

OTU

Region

130 – 138

9

Ubiquitin-conjugating enzyme E2 binding

Region

169 – 177

9

Ubiquitin-conjugating enzyme E2 binding

Region

189 – 195

7

Free ubiquitin binding

Region

206 – 213

8

Ubiquitin-conjugating enzyme E2 binding

Region

214 – 221

8

Free ubiquitin binding

Region

245 – 251

7

Free ubiquitin binding

Sites

Active site

88

1

Active site

91

1

Nucleophile

Active site

265

1

Binding site

221

1

Free ubiquitin

Binding site

235

1

Free ubiquitin

Binding site

237

1

Free ubiquitin

Binding site

261

1

Free ubiquitin

Binding site

266

1

Free ubiquitin

Site

23

1

Required for proximal ubiquitin-binding

Amino acid modifications

Modified residue

16

1

Phosphoserine Ref.8

Natural variations

Alternative sequence

1 – 112

112

MAAEE…SKELQ → MMKPSWLSRTEFSKRLLCRT LWCQSGWSSRSYTRSMLKMT TSINRRSRTSTKSTRTSARP GLTATVSIGLSDSPTWRHCW MTARSCSGEKGGHWAPRQVG VYLLPGRVGCVSSRVSPSFP GDGLDSGLARRGSAVSALAS GLVEEPMLGPPFHPTP in isoform 2.

VSP_009464

Experimental info

Mutagenesis

23

1

C → A: Abolishes only ubiquitin-vinylsulfone adduct formation. Ref.10

Mutagenesis

33

1

Q → R: Impairs inhibition of UBE2N/UBC13. Ref.14

Mutagenesis

37

1

I → T: Impairs inhibition of UBE2N/UBC13. Ref.14

Mutagenesis

39

1

Q → L: Does not affect activity in DNA repair and ability to inhibit UBE2N/UBC13. Ref.14

Mutagenesis

87

1

P → G: Slightly improves ability to cleave 'K63'-linked ubiquitin. Ref.13

Mutagenesis

88

1

D → E: Abolishes hydrolase activity in vitro. Abolishes ability to inhibit RNF168; when associated with S-91 and A-265. Ref.1 Ref.11

Mutagenesis

91

1

C → A: Prevents RNF128 autoubiquitination, and stabilizes RNF128 in vivo. Abolishes both ubiquitin-binding and adduct formation with ubiquitin-vinylsulfone. Ref.1 Ref.2 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14

Mutagenesis

91

1

C → 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. Ref.1 Ref.2 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14

Mutagenesis

116

1

A → T: Does not affect ability to inhibit UBE2N/UBC13. Ref.14

Mutagenesis

134

1

T → R: Impairs inhibition of UBE2N/UBC13. Ref.14

Mutagenesis

137

1

D → G: Impairs inhibition of UBE2N/UBC13. Ref.14

Mutagenesis

176

1

R → L: No effect on RNF128. Ref.2

Mutagenesis

190

1

F → S: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13. Ref.14

Mutagenesis

212

1

C → A: No effect on RNF128. Ref.2 Ref.10

Mutagenesis

261

1

Y → H: Impairs inhibition of UBE2N/UBC13. Ref.14

Mutagenesis

263

1

P → L: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13. Ref.14

Mutagenesis

265

1

H → A: Abolishes ability to inhibit RNF168; when associated with A-88 and S-91. Ref.1 Ref.11

Mutagenesis

265

1

H → R: Abolishes hydrolase activity in vitro. Ref.1 Ref.11

Sequence conflict

61

1

Y → C in AAH10368. Ref.6

Sequence conflict

151

1

K → R in BAA90956. Ref.4

Secondary structure

1

.

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271

Helix Strand Turn

Details...

Helix

27 – 31

5

Helix

33 – 44

12

Beta strand

47 – 53

7

Helix

54 – 60

7

Helix

66 – 75

10

Turn

76 – 78

3

Beta strand

81 – 83

3

Beta strand

87 – 89

3

Helix

91 – 104

14

Helix

108 – 127

20

Helix

132 – 150

19

Helix

155 – 162

8

Helix

165 – 185

21

Helix

187 – 190

4

Helix

191 – 193

3

Beta strand

194 – 197

4

Helix

200 – 207

8

Helix

217 – 227

11

Beta strand

231 – 235

5

Beta strand

240 – 242

3

Beta strand

245 – 250

6

Beta strand

256 – 262

7

Beta strand

265 – 270

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Otubain-1) [UniParc]. Last modified March 1, 2004. Version 2. Checksum: 63188EE1DC5FD66F	FASTA	271	31,284
	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
	Isoform 2 (ARF-1) [UniParc]. Checksum: 3B37EB8F1B3B2404	FASTA	315	35,285
	10 20 30 40 50 60 MMKPSWLSRT EFSKRLLCRT LWCQSGWSSR SYTRSMLKMT TSINRRSRTS TKSTRTSARP 70 80 90 100 110 120 GLTATVSIGL SDSPTWRHCW MTARSCSGEK GGHWAPRQVG VYLLPGRVGC VSSRVSPSFP 130 140 150 160 170 180 GDGLDSGLAR RGSAVSALAS GLVEEPMLGP PFHPTPRFKA VSAKSKEDLV SQGFTEFTIE 190 200 210 220 230 240 DFHNTFMDLI EQVEKQTSVA DLLASFNDQS TSDYLVVYLR LLTSGYLQRE SKFFEHFIEG 250 260 270 280 290 300 GRTVKEFCQQ EVEPMCKESD HIHIIALAQA LSVSIQVEYM DRGEGGTTNP HIFPEGSEPK 310 VYLLYRPGHY DILYK

References

	« Hide 'large scale' referencesShow '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] [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]	"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] [Europe PMC] [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. , 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]	"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. , 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] [Europe PMC] [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] [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]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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.
[10]	"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.
[11]	"Non-canonical inhibition of DNA damage-dependent ubiquitination by OTUB1." Nakada S., Tai I., Panier S., Al-Hakim A., Iemura S., Juang Y.C., O'Donnell L., Kumakubo A., Munro M., Sicheri F., Gingras A.C., Natsume T., Suda T., Durocher D. Nature 466:941-946(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN INHIBITION OF RNF168, INTERACTION WITH UBE2N/UBC13, MUTAGENESIS OF ASP-88; CYS-91 AND HIS-265.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"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.
[14]	"OTUB1 co-opts Lys48-linked ubiquitin recognition to suppress E2 enzyme function." Juang Y.C., Landry M.C., Sanches M., Vittal V., Leung C.C., Ceccarelli D.F., Mateo A.R., Pruneda J.N., Mao D.Y., Szilard R.K., Orlicky S., Munro M., Brzovic P.S., Klevit R.E., Sicheri F., Durocher D. Mol. Cell 45:384-397(2012) [PubMed] [Europe PMC] [Abstract] 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.
[15]	"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.
+	Additional computationally mapped references.

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.

IPI

IPI00409750.
IPI00939174.

RefSeq

NP_060140.2. NM_017670.2.

UniGene

Hs.473788.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q96FW1.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41158N.

IntAct

Q96FW1. 9 interactions.

MINT

MINT-5001867.

STRING

9606.ENSP00000301453.

Protein family/group databases

MEROPS

C65.001.

PTM databases

PhosphoSite

Q96FW1.

Polymorphism databases

DMDM

44888286.

Proteomic databases

PaxDb

Q96FW1.

PRIDE

Q96FW1.

Protocols and materials databases

DNASU

55611.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000428192; ENSP00000402551; ENSG00000167770.
ENST00000538426; ENSP00000444357; ENSG00000167770.

GeneID

55611.

KEGG

hsa:55611.

UCSC

uc001nyf.1. human.
uc001nyg.1. human.

Organism-specific databases

CTD

55611.

GeneCards

GC11P063753.

HGNC

HGNC:23077. OTUB1.

HPA

HPA039176.

MIM

608337. gene.

neXtProt

NX_Q96FW1.

PharmGKB

PA134988141.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG267426.

HOVERGEN

HBG053383.

InParanoid

Q96FW1.

KO

K09602.

OrthoDB

EOG47H5QS.

PhylomeDB

Q96FW1.

Gene expression databases

ArrayExpress

Q96FW1.

Bgee

Q96FW1.

CleanEx

HS_OTUB1.

Genevestigator

Q96FW1.

GermOnline

ENSG00000167770. Homo sapiens.

Family and domain databases

InterPro

IPR003323. OTU.
IPR019400. Peptidase_C65_otubain.
IPR016615. Ubiquitin_thioesterase_Otubain.
[Graphical view]

Pfam

PF10275. Peptidase_C65. 1 hit.
[Graphical view]

PIRSF

PIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.

PROSITE

PS50802. OTU. 1 hit.
[Graphical view]

ProtoNet

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Other

ChiTaRS

OTUB1. human.

EvolutionaryTrace

Q96FW1.

GenomeRNAi

55611.

NextBio

60179.

SOURCE

Search...

Entry information

Entry name

OTUB1_HUMAN

Accession

Primary (citable) accession number: Q96FW1
Secondary accession number(s): Q32Q78 , Q96II3, Q9NXQ4, Q9P0B8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	March 1, 2004
Last modified:	May 1, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.