| UniProt ID | OTUB1_HUMAN | |
|---|---|---|
| UniProt AC | Q96FW1 | |
| Protein Name | Ubiquitin thioesterase OTUB1 | |
| Gene Name | OTUB1 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 271 | |
| Subcellular Localization | Cytoplasm. | |
| Protein Description | 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.. | |
| Protein Sequence | MAAEEPQQQKQEPLGSDSEGVNCLAYDEAIMAQQDRIQQEIAVQNPLVSERLELSVLYKEYAEDDNIYQQKIKDLHKKYSYIRKTRPDGNCFYRAFGFSHLEALLDDSKELQRFKAVSAKSKEDLVSQGFTEFTIEDFHNTFMDLIEQVEKQTSVADLLASFNDQSTSDYLVVYLRLLTSGYLQRESKFFEHFIEGGRTVKEFCQQEVEPMCKESDHIHIIALAQALSVSIQVEYMDRGEGGTTNPHIFPEGSEPKVYLLYRPGHYDILYK | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 2 | Acetylation | ------MAAEEPQQQ ------CCCCCHHHH | 24.47 | 22814378 | |
| 10 | Sumoylation | AEEPQQQKQEPLGSD CCCHHHHCCCCCCCC | 52.90 | - | |
| 13 (in isoform 2) | Phosphorylation | - | 39.26 | 30631047 | |
| 16 | Phosphorylation | QKQEPLGSDSEGVNC HCCCCCCCCCCCCCC | 45.72 | 22167270 | |
| 18 | Phosphorylation | QEPLGSDSEGVNCLA CCCCCCCCCCCCCHH | 37.64 | 21945579 | |
| 26 | Phosphorylation | EGVNCLAYDEAIMAQ CCCCCHHHHHHHHHH | 11.02 | 21945579 | |
| 31 | Sulfoxidation | LAYDEAIMAQQDRIQ HHHHHHHHHHHHHHH | 3.38 | 30846556 | |
| 35 (in isoform 2) | Phosphorylation | - | 37.25 | 22199227 | |
| 40 (in isoform 2) | Phosphorylation | - | 19.28 | 22199227 | |
| 41 (in isoform 2) | Phosphorylation | - | 3.85 | 22199227 | |
| 42 (in isoform 2) | Phosphorylation | - | 8.97 | 22199227 | |
| 55 | Phosphorylation | VSERLELSVLYKEYA HHHHHHHHHHHHHHH | 10.74 | 29523821 | |
| 58 | Phosphorylation | RLELSVLYKEYAEDD HHHHHHHHHHHHCCC | 10.30 | 28102081 | |
| 59 | Ubiquitination | LELSVLYKEYAEDDN HHHHHHHHHHHCCCC | 39.84 | 21906983 | |
| 65 (in isoform 2) | Phosphorylation | - | 34.63 | 22210691 | |
| 68 | Phosphorylation | YAEDDNIYQQKIKDL HHCCCCCCHHHHHHH | 15.90 | - | |
| 71 | Ubiquitination | DDNIYQQKIKDLHKK CCCCCHHHHHHHHHH | 35.88 | 21890473 | |
| 71 (in isoform 1) | Ubiquitination | - | 35.88 | 21890473 | |
| 71 | Acetylation | DDNIYQQKIKDLHKK CCCCCHHHHHHHHHH | 35.88 | 26822725 | |
| 71 | 2-Hydroxyisobutyrylation | DDNIYQQKIKDLHKK CCCCCHHHHHHHHHH | 35.88 | - | |
| 73 | Ubiquitination | NIYQQKIKDLHKKYS CCCHHHHHHHHHHHH | 62.36 | - | |
| 73 (in isoform 2) | Phosphorylation | - | 62.36 | 22210691 | |
| 75 (in isoform 2) | Phosphorylation | - | 5.61 | 22210691 | |
| 84 (in isoform 1) | Ubiquitination | - | 39.05 | 21890473 | |
| 84 | Ubiquitination | KKYSYIRKTRPDGNC HHHHHHCCCCCCCCH | 39.05 | 21890473 | |
| 108 | Phosphorylation | LEALLDDSKELQRFK HHHHHCCCHHHHHHH | 27.91 | 28348404 | |
| 109 (in isoform 1) | Ubiquitination | - | 70.23 | 21890473 | |
| 109 | Ubiquitination | EALLDDSKELQRFKA HHHHCCCHHHHHHHH | 70.23 | 20639865 | |
| 115 | 2-Hydroxyisobutyrylation | SKELQRFKAVSAKSK CHHHHHHHHHCCCCH | 50.49 | - | |
| 161 | Phosphorylation | SVADLLASFNDQSTS CHHHHHHHCCCCCCC | 25.26 | - | |
| 174 | Phosphorylation | TSDYLVVYLRLLTSG CCHHHHHHHHHHHHC | 4.42 | 24719451 | |
| 188 (in isoform 1) | Ubiquitination | - | 49.69 | 21890473 | |
| 188 | Sumoylation | GYLQRESKFFEHFIE CHHHHHHHHHHHHHH | 49.69 | 19608861 | |
| 188 | Ubiquitination | GYLQRESKFFEHFIE CHHHHHHHHHHHHHH | 49.69 | 2189047 | |
| 188 | Acetylation | GYLQRESKFFEHFIE CHHHHHHHHHHHHHH | 49.69 | 19608861 | |
| 201 | Ubiquitination | IEGGRTVKEFCQQEV HHCCHHHHHHHHHHH | 44.45 | - | |
| 201 | Acetylation | IEGGRTVKEFCQQEV HHCCHHHHHHHHHHH | 44.45 | 26051181 | |
| 232 (in isoform 2) | Ubiquitination | - | 17.93 | 21890473 | |
| 245 (in isoform 2) | Ubiquitination | - | 26.45 | - | |
| 258 | Phosphorylation | EGSEPKVYLLYRPGH CCCCCEEEEEECCCC | 9.34 | 28152594 | |
| 261 | Phosphorylation | EPKVYLLYRPGHYDI CCEEEEEECCCCCCC | 16.50 | 28152594 | |
| 266 | Phosphorylation | LLYRPGHYDILYK-- EEECCCCCCCCCC-- | 15.59 | 28152594 |
| Modified Location | Modified Residue | Modification | Function | Reference | ||
|---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of OTUB1_HUMAN !! | ||||||
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of OTUB1_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| There are no disease associations of PTM sites. | ||||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Acetylation | |
| Reference | PubMed |
| "Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY. | |
| "Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-188, AND MASS SPECTROMETRY. | |
| Phosphorylation | |
| Reference | PubMed |
| "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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, AND MASSSPECTROMETRY. | |
