ID OTUB1_HUMAN Reviewed; 271 AA. AC Q96FW1; Q32Q78; Q96II3; Q9NXQ4; Q9P0B8; DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2004, sequence version 2. DT 27-MAR-2024, entry version 194. DE RecName: Full=Ubiquitin thioesterase OTUB1; DE EC=3.4.19.12 {ECO:0000269|PubMed:23827681}; DE AltName: Full=Deubiquitinating enzyme OTUB1; DE AltName: Full=OTU domain-containing ubiquitin aldehyde-binding protein 1; DE AltName: Full=Otubain-1; DE Short=hOTU1; DE AltName: Full=Ubiquitin-specific-processing protease OTUB1; GN Name=OTUB1; Synonyms=OTB1, OTU1; ORFNames=HSPC263; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS RP SPECTROMETRY, FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-88; RP CYS-91 AND HIS-265. RC TISSUE=Cervix carcinoma; RX PubMed=12704427; DOI=10.1038/sj.embor.embor824; RA Balakirev M.Y., Tcherniuk S.O., Jaquinod M., Chroboczek J.; RT "Otubains: a new family of cysteine proteases in the ubiquitin pathway."; RL EMBO Rep. 4:517-522(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING, RP FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH RNF128 AND USP8, AND RP MUTAGENESIS OF CYS-91; ARG-176 AND CYS-212. RX PubMed=14661020; DOI=10.1038/ni1017; RA Soares L., Seroogy C., Skrenta H., Anandasabapathy N., Lovelace P., RA Chung C.D., Engleman E., Fathman C.G.; RT "Two isoforms of otubain 1 regulate T cell anergy via GRAIL."; RL Nat. Immunol. 5:45-54(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PARTIAL PROTEIN SEQUENCE, AND FUNCTION. RX PubMed=12401499; DOI=10.1016/s1074-5521(02)00248-x; RA Borodovsky A., Ovaa H., Kolli N., Gan-Erdene T., Wilkinson K.D., RA Ploegh H.L., Kessler B.M.; RT "Chemistry-based functional proteomics reveals novel members of the RT deubiquitinating enzyme family."; RL Chem. Biol. 9:1149-1159(2002). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [10] RP FUNCTION, AND MUTAGENESIS OF CYS-91. RX PubMed=19383985; DOI=10.1074/jbc.m109.007484; RA Stanisic V., Malovannaya A., Qin J., Lonard D.M., O'Malley B.W.; RT "OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) RT deubiquitinates estrogen receptor (ER) alpha and affects ERalpha RT transcriptional activity."; RL J. Biol. Chem. 284:16135-16145(2009). RN [11] RP FUNCTION, UBIQUITIN-BINDING, DOMAIN, AND MUTAGENESIS OF CYS-23; CYS-91 AND RP CYS-212. RX PubMed=19211026; DOI=10.1016/j.jmb.2008.12.085; RA Wang T., Yin L., Cooper E.M., Lai M.-Y., Dickey S., Pickart C.M., RA Fushman D., Wilkinson K.D., Cohen R.E., Wolberger C.; RT "Evidence for bidentate substrate binding as the basis for the K48 linkage RT specificity of otubain 1."; RL J. Mol. Biol. 386:1011-1023(2009). RN [12] RP FUNCTION IN INHIBITION OF RNF168, INTERACTION WITH UBE2N/UBC13, AND RP MUTAGENESIS OF ASP-88; CYS-91 AND HIS-265. RX PubMed=20725033; DOI=10.1038/nature09297; RA Nakada S., Tai I., Panier S., Al-Hakim A., Iemura S., Juang Y.C., RA O'Donnell L., Kumakubo A., Munro M., Sicheri F., Gingras A.C., Natsume T., RA Suda T., Durocher D.; RT "Non-canonical inhibition of DNA damage-dependent ubiquitination by RT OTUB1."; RL Nature 466:941-946(2010). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [15] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23827681; DOI=10.1016/j.cell.2013.05.046; RA Mevissen T.E., Hospenthal M.K., Geurink P.P., Elliott P.R., Akutsu M., RA Arnaudo N., Ekkebus R., Kulathu Y., Wauer T., El Oualid F., Freund S.M., RA Ovaa H., Komander D.; RT "OTU deubiquitinases reveal mechanisms of linkage specificity and enable RT ubiquitin chain restriction analysis."; RL Cell 154:169-184(2013). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP FUNCTION, AND MUTAGENESIS OF CYS-23; ASP-88 AND CYS-91. RX PubMed=29382726; DOI=10.1074/jbc.m117.809533; RA Zhao L., Wang X., Yu Y., Deng L., Chen L., Peng X., Jiao C., Gao G., RA Tan X., Pan W., Ge X., Wang P.; RT "OTUB1 protein suppresses mTOR complex 1 (mTORC1) activity by RT deubiquitinating the mTORC1 inhibitor DEPTOR."; RL J. Biol. Chem. 293:4883-4892(2018). RN [18] RP FUNCTION, INTERACTION WITH UBE2D1; UBE2W AND UBE2N, PHOSPHORYLATION AT RP TYR-26, AND MUTAGENESIS OF TYR-26; ASP-88; CYS-91 AND HIS-265. RX PubMed=35927303; DOI=10.1038/s41418-022-01047-3; RA Seo S.U., Woo S.M., Kim M.W., Lee E.W., Min K.J., Kwon T.K.; RT "Phosphorylation of OTUB1 at Tyr 26 stabilizes the mTORC1 component, RT Raptor."; RL Cell Death Differ. 30:82-93(2023). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS) OF 40-271, FUNCTION, INTERACTION RP WITH FUS AND RACK1, MUTAGENESIS OF PRO-87 AND CYS-91, AND ACTIVE SITE. RX PubMed=18954305; DOI=10.1042/bj20081318; RA Edelmann M.J., Iphoefer A., Akutsu M., Altun M., di Gleria K., Kramer H.B., RA Fiebiger E., Dhe-Paganon S., Kessler B.M.; RT "Structural basis and specificity of human otubain 1-mediated RT deubiquitination."; RL Biochem. J. 418:379-390(2009). RN [20] RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 25-271 IN COMPLEX WITH UBE2V2 AND RP UBE2N, FREE UBIQUITIN-BINDING, ACTIVITY REGULATION, AND MUTAGENESIS OF RP GLN-33; ILE-37; GLN-39; CYS-91; ALA-116; THR-134; ASP-137; PHE-190; TYR-261 RP AND PRO-263. RX PubMed=22325355; DOI=10.1016/j.molcel.2012.01.011; RA Juang Y.C., Landry M.C., Sanches M., Vittal V., Leung C.C., RA Ceccarelli D.F., Mateo A.R., Pruneda J.N., Mao D.Y., Szilard R.K., RA Orlicky S., Munro M., Brzovic P.S., Klevit R.E., Sicheri F., Durocher D.; RT "OTUB1 co-opts Lys48-linked ubiquitin recognition to suppress E2 enzyme RT function."; RL Mol. Cell 45:384-397(2012). RN [21] RP X-RAY CRYSTALLOGRAPHY (3.11 ANGSTROMS) OF 1-45 IN COMPLEX WITH UBE2N AND RP UBIQUITIN, ACTIVITY REGULATION, AND FREE UBIQUITIN-BINDING. RX PubMed=22367539; DOI=10.1038/nature10911; RA Wiener R., Zhang X., Wang T., Wolberger C.; RT "The mechanism of OTUB1-mediated inhibition of ubiquitination."; RL Nature 483:618-622(2012). CC -!- FUNCTION: Hydrolase that can specifically remove 'Lys-48'-linked CC conjugated ubiquitin from proteins and plays an important regulatory CC role at the level of protein turnover by preventing degradation CC (PubMed:12704427, PubMed:14661020, PubMed:12401499, PubMed:23827681). CC Regulator of T-cell anergy, a phenomenon that occurs when T-cells are CC rendered unresponsive to antigen rechallenge and no longer respond to CC their cognate antigen (PubMed:14661020). Acts via its interaction with CC RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy CC (PubMed:14661020). Isoform 1 destabilizes RNF128, leading to prevent CC anergy (PubMed:14661020). In contrast, isoform 2 stabilizes RNF128 and CC promotes anergy (PubMed:14661020). Surprisingly, it regulates RNF128- CC mediated ubiquitination, but does not deubiquitinate polyubiquitinated CC RNF128 (PubMed:14661020). Deubiquitinates estrogen receptor alpha CC (ESR1) (PubMed:19383985). Mediates deubiquitination of 'Lys-48'-linked CC polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains CC (PubMed:19211026, PubMed:23827681, PubMed:18954305). Not able to cleave CC di-ubiquitin (PubMed:23827681, PubMed:18954305). Also capable of CC removing NEDD8 from NEDD8 conjugates, but with a much lower preference CC compared to 'Lys-48'-linked ubiquitin (PubMed:23827681, CC PubMed:18954305). {ECO:0000269|PubMed:12401499, CC ECO:0000269|PubMed:12704427, ECO:0000269|PubMed:14661020, CC ECO:0000269|PubMed:18954305, ECO:0000269|PubMed:19211026, CC ECO:0000269|PubMed:19383985, ECO:0000269|PubMed:23827681}. CC -!- FUNCTION: Plays a key non-catalytic role in DNA repair regulation by CC inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that CC promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA CC damage sites (PubMed:20725033, PubMed:22325355). Inhibits RNF168 CC independently of ubiquitin thioesterase activity by binding and CC inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting CC spreading of 'Lys-63'-linked histone H2A and H2AX marks CC (PubMed:20725033, PubMed:22325355). Inhibition occurs by binding to CC free ubiquitin: free ubiquitin acts as an allosteric regulator that CC increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1 CC (PubMed:20725033, PubMed:22325355). The OTUB1-UBE2N/UBC13-free CC ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'- CC linked di-ubiquitin chain (PubMed:20725033, PubMed:22325355). Acts as a CC regulator of mTORC1 and mTORC2 complexes (PubMed:29382726, CC PubMed:35927303). When phosphorylated at Tyr-26, acts as an activator CC of the mTORC1 complex by mediating deubiquitination of RPTOR via a non- CC catalytic process: acts by binding and inhibiting the activity of the CC ubiquitin-conjugating enzyme E2 (UBE2D1/UBCH5A, UBE2W/UBC16 and CC UBE2N/UBC13), thereby preventing ubiquitination of RPTOR CC (PubMed:35927303). Can also act as an inhibitor of the mTORC1 and CC mTORC2 complexes in response to amino acids by mediating non-catalytic CC deubiquitination of DEPTOR (PubMed:29382726). CC {ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, CC ECO:0000269|PubMed:29382726, ECO:0000269|PubMed:35927303}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:23827681}; CC -!- ACTIVITY REGULATION: By free ubiquitin: binding of free ubiquitin CC triggers conformational changes in the OTU domain and formation of a CC ubiquitin-binding helix in the N-terminus, promoting binding of the CC conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1. CC {ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:22367539}. CC -!- SUBUNIT: Interacts with FUS and RACK1 (PubMed:18954305). Interacts with CC UBE2D1/UBCH5A, UBE2W/UBC16 and UBE2N/UBC13 (PubMed:20725033, CC PubMed:35927303, PubMed:22325355, PubMed:22367539). CC {ECO:0000269|PubMed:18954305, ECO:0000269|PubMed:20725033, CC ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:22367539, CC ECO:0000269|PubMed:35927303}. CC -!- SUBUNIT: [Isoform 1]: Interacts with RNF128 (PubMed:14661020). Forms a CC ternary complex with RNF128 and USP8 (PubMed:14661020). Interacts with CC the C-terminal UCH catalytic domain of USP8 (PubMed:14661020). CC {ECO:0000269|PubMed:14661020}. CC -!- SUBUNIT: [Isoform 2]: Interacts with RNF128 (PubMed:14661020). Does not CC associate with USP8 (PubMed:14661020). {ECO:0000269|PubMed:14661020}. CC -!- INTERACTION: CC Q96FW1; P01023: A2M; NbExp=3; IntAct=EBI-1058491, EBI-640741; CC Q96FW1; P05067: APP; NbExp=3; IntAct=EBI-1058491, EBI-77613; CC Q96FW1; P54253: ATXN1; NbExp=6; IntAct=EBI-1058491, EBI-930964; CC Q96FW1; P46379-2: BAG6; NbExp=3; IntAct=EBI-1058491, EBI-10988864; CC Q96FW1; Q13490: BIRC2; NbExp=3; IntAct=EBI-1058491, EBI-514538; CC Q96FW1; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-1058491, EBI-2837444; CC Q96FW1; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-1058491, EBI-25840379; CC Q96FW1; G5E9A7: DMWD; NbExp=3; IntAct=EBI-1058491, EBI-10976677; CC Q96FW1; O75190-2: DNAJB6; NbExp=3; IntAct=EBI-1058491, EBI-12593112; CC Q96FW1; O14645: DNALI1; NbExp=3; IntAct=EBI-1058491, EBI-395638; CC Q96FW1; P50570-2: DNM2; NbExp=3; IntAct=EBI-1058491, EBI-10968534; CC Q96FW1; P35637: FUS; NbExp=3; IntAct=EBI-1058491, EBI-400434; CC Q96FW1; P14136: GFAP; NbExp=3; IntAct=EBI-1058491, EBI-744302; CC Q96FW1; Q53GS7: GLE1; NbExp=3; IntAct=EBI-1058491, EBI-1955541; CC Q96FW1; P28799: GRN; NbExp=3; IntAct=EBI-1058491, EBI-747754; CC Q96FW1; P07686: HEXB; NbExp=3; IntAct=EBI-1058491, EBI-7133736; CC Q96FW1; Q9NWT6: HIF1AN; NbExp=5; IntAct=EBI-1058491, EBI-745632; CC Q96FW1; P04792: HSPB1; NbExp=3; IntAct=EBI-1058491, EBI-352682; CC Q96FW1; O43464: HTRA2; NbExp=3; IntAct=EBI-1058491, EBI-517086; CC Q96FW1; Q9UMF0: ICAM5; NbExp=3; IntAct=EBI-1058491, EBI-6398041; CC Q96FW1; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-1058491, EBI-1055254; CC Q96FW1; O60333-2: KIF1B; NbExp=3; IntAct=EBI-1058491, EBI-10975473; CC Q96FW1; O14901: KLF11; NbExp=3; IntAct=EBI-1058491, EBI-948266; CC Q96FW1; Q00987: MDM2; NbExp=5; IntAct=EBI-1058491, EBI-389668; CC Q96FW1; P51608: MECP2; NbExp=3; IntAct=EBI-1058491, EBI-1189067; CC Q96FW1; P19404: NDUFV2; NbExp=3; IntAct=EBI-1058491, EBI-713665; CC Q96FW1; P35240-4: NF2; NbExp=3; IntAct=EBI-1058491, EBI-1014514; CC Q96FW1; Q8N6M0: OTUD6B; NbExp=2; IntAct=EBI-1058491, EBI-2510892; CC Q96FW1; Q99497: PARK7; NbExp=4; IntAct=EBI-1058491, EBI-1164361; CC Q96FW1; O60260-5: PRKN; NbExp=3; IntAct=EBI-1058491, EBI-21251460; CC Q96FW1; P60891: PRPS1; NbExp=3; IntAct=EBI-1058491, EBI-749195; CC Q96FW1; P49768-2: PSEN1; NbExp=3; IntAct=EBI-1058491, EBI-11047108; CC Q96FW1; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-1058491, EBI-396669; CC Q96FW1; P37840: SNCA; NbExp=3; IntAct=EBI-1058491, EBI-985879; CC Q96FW1; P00441: SOD1; NbExp=3; IntAct=EBI-1058491, EBI-990792; CC Q96FW1; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-1058491, EBI-5235340; CC Q96FW1; Q13148: TARDBP; NbExp=8; IntAct=EBI-1058491, EBI-372899; CC Q96FW1; P04637: TP53; NbExp=8; IntAct=EBI-1058491, EBI-366083; CC Q96FW1; O14773: TPP1; NbExp=3; IntAct=EBI-1058491, EBI-2800203; CC Q96FW1; Q86WV8: TSC1; NbExp=3; IntAct=EBI-1058491, EBI-12806590; CC Q96FW1; P02766: TTR; NbExp=4; IntAct=EBI-1058491, EBI-711909; CC Q96FW1; P22314: UBA1; NbExp=4; IntAct=EBI-1058491, EBI-709688; CC Q96FW1; P0CG47: UBB; NbExp=3; IntAct=EBI-1058491, EBI-413034; CC Q96FW1; P51668: UBE2D1; NbExp=14; IntAct=EBI-1058491, EBI-743540; CC Q96FW1; P62837: UBE2D2; NbExp=16; IntAct=EBI-1058491, EBI-347677; CC Q96FW1; P61077: UBE2D3; NbExp=14; IntAct=EBI-1058491, EBI-348268; CC Q96FW1; Q9Y2X8: UBE2D4; NbExp=9; IntAct=EBI-1058491, EBI-745527; CC Q96FW1; P51965: UBE2E1; NbExp=3; IntAct=EBI-1058491, EBI-348546; CC Q96FW1; Q96LR5: UBE2E2; NbExp=8; IntAct=EBI-1058491, EBI-2129763; CC Q96FW1; Q969T4: UBE2E3; NbExp=8; IntAct=EBI-1058491, EBI-348496; CC Q96FW1; P40337-2: VHL; NbExp=3; IntAct=EBI-1058491, EBI-12157263; CC Q96FW1; O76024: WFS1; NbExp=3; IntAct=EBI-1058491, EBI-720609; CC Q96FW1; Q56921: ypkA; Xeno; NbExp=5; IntAct=EBI-1058491, EBI-8022937; CC Q96FW1; Q9RI12: ypkA; Xeno; NbExp=3; IntAct=EBI-1058491, EBI-2849107; CC Q96FW1-1; P61088: UBE2N; NbExp=5; IntAct=EBI-15972141, EBI-1052908; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:B2RYG6}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Otubain-1; CC IsoId=Q96FW1-1; Sequence=Displayed; CC Name=2; Synonyms=ARF-1; CC IsoId=Q96FW1-2; Sequence=VSP_009464; CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitous. Isoform 2 is expressed CC only in lymphoid tissues such as tonsils, lymph nodes and spleen, as CC well as peripheral blood mononuclear cells. CC {ECO:0000269|PubMed:12704427, ECO:0000269|PubMed:14661020}. CC -!- DOMAIN: In addition to ubiquitin-binding at the Cys-91 active site, a CC proximal ubiquitin-binding site is also present at Cys-23 Occupancy of CC the active site is needed to enable tight binding to the second site. CC Distinct binding sites for the ubiquitins may allow to discriminate CC among different isopeptide linkages (i.e. 'Lys-48'-, 'Lys-63'-linked CC polyubiquitin) in polyubiquitin substrates and achieve linkage-specific CC deubiquitination. {ECO:0000269|PubMed:19211026}. CC -!- PTM: Phosphorylation at Tyr-26 by SRC and SRMS promotes CC deubiquitination of RPTOR via a non-catalytic process. CC {ECO:0000269|PubMed:35927303}. CC -!- MISCELLANEOUS: In the structure described by PubMed:18954305, the His- CC 265 active site of the catalytic triad is located too far to interact CC directly with the active site Cys-91 (PubMed:18954305). A possible CC explanation is that OTUB1 is in inactive conformation in absence of CC ubiquitin and a conformation change may move His-265 in the proximity CC of Cys-91 in presence of ubiquitin substrate (PubMed:18954305). CC {ECO:0000269|PubMed:18954305}. CC -!- MISCELLANEOUS: [Isoform 2]: Lacks the catalytic sites for protease CC activity. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase C65 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF28941.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY177200; AAO27702.1; -; mRNA. DR EMBL; AF161381; AAF28941.1; ALT_INIT; mRNA. DR EMBL; AK000120; BAA90956.1; -; mRNA. DR EMBL; AP000721; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC007519; AAH07519.1; -; mRNA. DR EMBL; BC010368; AAH10368.1; -; mRNA. DR EMBL; BC107701; AAI07702.1; -; mRNA. DR CCDS; CCDS8055.1; -. [Q96FW1-1] DR RefSeq; NP_060140.2; NM_017670.2. [Q96FW1-1] DR PDB; 2ZFY; X-ray; 1.69 A; A=40-271. DR PDB; 3VON; X-ray; 3.15 A; A/H/O/V/c/j=45-271. DR PDB; 4DDG; X-ray; 3.30 A; A/B/C/J/K/L=25-271. DR PDB; 4DDI; X-ray; 3.80 A; A/B/C=25-271. DR PDB; 4DHZ; X-ray; 3.11 A; A=1-45. DR PDB; 4I6L; X-ray; 2.49 A; A=45-271. DR PDB; 4LDT; X-ray; 1.90 A; A=1-45. DR PDBsum; 2ZFY; -. DR PDBsum; 3VON; -. DR PDBsum; 4DDG; -. DR PDBsum; 4DDI; -. DR PDBsum; 4DHZ; -. DR PDBsum; 4I6L; -. DR PDBsum; 4LDT; -. DR AlphaFoldDB; Q96FW1; -. DR SMR; Q96FW1; -. DR BioGRID; 120751; 343. DR CORUM; Q96FW1; -. DR DIP; DIP-41158N; -. DR IntAct; Q96FW1; 373. DR MINT; Q96FW1; -. DR STRING; 9606.ENSP00000444357; -. DR BindingDB; Q96FW1; -. DR ChEMBL; CHEMBL4523428; -. DR GuidetoPHARMACOLOGY; 3208; -. DR MEROPS; C65.001; -. DR GlyGen; Q96FW1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96FW1; -. DR MetOSite; Q96FW1; -. DR PhosphoSitePlus; Q96FW1; -. DR SwissPalm; Q96FW1; -. DR BioMuta; OTUB1; -. DR DMDM; 44888286; -. DR CPTAC; CPTAC-244; -. DR CPTAC; CPTAC-245; -. DR EPD; Q96FW1; -. DR jPOST; Q96FW1; -. DR MassIVE; Q96FW1; -. DR MaxQB; Q96FW1; -. DR PaxDb; 9606-ENSP00000444357; -. DR PeptideAtlas; Q96FW1; -. DR ProteomicsDB; 76566; -. [Q96FW1-1] DR ProteomicsDB; 76567; -. [Q96FW1-2] DR Pumba; Q96FW1; -. DR Antibodypedia; 29104; 554 antibodies from 35 providers. DR CPTC; Q96FW1; 3 antibodies. DR DNASU; 55611; -. DR Ensembl; ENST00000428192.6; ENSP00000402551.2; ENSG00000167770.13. [Q96FW1-1] DR Ensembl; ENST00000538426.6; ENSP00000444357.1; ENSG00000167770.13. [Q96FW1-1] DR GeneID; 55611; -. DR KEGG; hsa:55611; -. DR MANE-Select; ENST00000538426.6; ENSP00000444357.1; NM_017670.3; NP_060140.2. DR UCSC; uc001nyf.2; human. [Q96FW1-1] DR AGR; HGNC:23077; -. DR CTD; 55611; -. DR DisGeNET; 55611; -. DR GeneCards; OTUB1; -. DR HGNC; HGNC:23077; OTUB1. DR HPA; ENSG00000167770; Low tissue specificity. DR MIM; 608337; gene. DR neXtProt; NX_Q96FW1; -. DR OpenTargets; ENSG00000167770; -. DR PharmGKB; PA134988141; -. DR VEuPathDB; HostDB:ENSG00000167770; -. DR eggNOG; KOG3991; Eukaryota. DR GeneTree; ENSGT00390000006979; -. DR InParanoid; Q96FW1; -. DR OrthoDB; 148019at2759; -. DR PhylomeDB; Q96FW1; -. DR TreeFam; TF314145; -. DR PathwayCommons; Q96FW1; -. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases. DR SignaLink; Q96FW1; -. DR SIGNOR; Q96FW1; -. DR BioGRID-ORCS; 55611; 53 hits in 1170 CRISPR screens. DR ChiTaRS; OTUB1; human. DR EvolutionaryTrace; Q96FW1; -. DR GeneWiki; OTUB1; -. DR GenomeRNAi; 55611; -. DR Pharos; Q96FW1; Tbio. DR PRO; PR:Q96FW1; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q96FW1; Protein. DR Bgee; ENSG00000167770; Expressed in right frontal lobe and 212 other cell types or tissues. DR ExpressionAtlas; Q96FW1; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0019784; F:deNEDDylase activity; IDA:UniProtKB. DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0055105; F:ubiquitin-protein transferase inhibitor activity; IDA:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:2000780; P:negative regulation of double-strand break repair; IMP:UniProtKB. DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IDA:UniProtKB. DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB. DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd22763; OTUB1; 1. DR Gene3D; 3.30.200.60; Peptidase C65 Otubain, subdomain 1; 1. DR Gene3D; 1.20.1300.20; Peptidase C65 Otubain, subdomain 2; 1. DR InterPro; IPR003323; OTU_dom. DR InterPro; IPR016615; Otubain. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR019400; Peptidase_C65_otubain. DR InterPro; IPR042468; Peptidase_C65_otubain_sub1. DR InterPro; IPR042467; Peptidase_C65_otubain_sub2. DR PANTHER; PTHR12931:SF19; UBIQUITIN THIOESTERASE OTUB1; 1. DR PANTHER; PTHR12931; UBIQUITIN THIOLESTERASE PROTEIN OTUB; 1. DR Pfam; PF10275; Peptidase_C65; 1. DR PIRSF; PIRSF013503; Ubiquitin_thioesterase_Otubain; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR PROSITE; PS50802; OTU; 1. DR Genevisible; Q96FW1; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Adaptive immunity; Alternative splicing; KW Cytoplasm; Direct protein sequencing; DNA damage; DNA repair; Hydrolase; KW Immunity; Phosphoprotein; Protease; Reference proteome; Thiol protease; KW Ubl conjugation pathway. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..271 FT /note="Ubiquitin thioesterase OTUB1" FT /id="PRO_0000221008" FT DOMAIN 80..271 FT /note="OTU" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139" FT REGION 130..138 FT /note="Ubiquitin-conjugating enzyme E2 binding" FT /evidence="ECO:0000269|PubMed:22325355" FT REGION 169..177 FT /note="Ubiquitin-conjugating enzyme E2 binding" FT /evidence="ECO:0000269|PubMed:22325355" FT REGION 189..195 FT /note="Free ubiquitin binding" FT /evidence="ECO:0000269|PubMed:22325355, FT ECO:0000269|PubMed:22367539, ECO:0007744|PDB:4DHZ" FT REGION 206..213 FT /note="Ubiquitin-conjugating enzyme E2 binding" FT /evidence="ECO:0000269|PubMed:22325355, FT ECO:0000269|PubMed:22367539, ECO:0007744|PDB:4DHZ" FT REGION 214..221 FT /note="Free ubiquitin binding" FT /evidence="ECO:0000269|PubMed:22325355, FT ECO:0000269|PubMed:22367539, ECO:0007744|PDB:4DHZ" FT REGION 245..251 FT /note="Free ubiquitin binding" FT /evidence="ECO:0000269|PubMed:22325355, FT ECO:0000269|PubMed:22367539, ECO:0007744|PDB:4DHZ" FT ACT_SITE 88 FT /evidence="ECO:0000269|PubMed:22367539, FT ECO:0007744|PDB:4DHZ" FT ACT_SITE 91 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:22325355, FT ECO:0000305|PubMed:18954305" FT ACT_SITE 265 FT /evidence="ECO:0000269|PubMed:22325355, FT ECO:0000305|PubMed:18954305" FT SITE 23 FT /note="Required for proximal ubiquitin-binding" FT /evidence="ECO:0000269|PubMed:19211026" FT SITE 221 FT /note="Interacts with free ubiquitin" FT /evidence="ECO:0000269|PubMed:22325355" FT SITE 235 FT /note="Interacts with free ubiquitin" FT /evidence="ECO:0000269|PubMed:22325355" FT SITE 237 FT /note="Interacts with free ubiquitin" FT /evidence="ECO:0000269|PubMed:22325355" FT SITE 261 FT /note="Interacts with free ubiquitin" FT /evidence="ECO:0000269|PubMed:22325355" FT SITE 266 FT /note="Interacts with free ubiquitin" FT /evidence="ECO:0000269|PubMed:22325355, FT ECO:0000269|PubMed:22367539, ECO:0007744|PDB:4DHZ" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT MOD_RES 16 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 26 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:35927303" FT VAR_SEQ 1..112 FT /note="MAAEEPQQQKQEPLGSDSEGVNCLAYDEAIMAQQDRIQQEIAVQNPLVSERL FT ELSVLYKEYAEDDNIYQQKIKDLHKKYSYIRKTRPDGNCFYRAFGFSHLEALLDDSKEL FT Q -> MMKPSWLSRTEFSKRLLCRTLWCQSGWSSRSYTRSMLKMTTSINRRSRTSTKST FT RTSARPGLTATVSIGLSDSPTWRHCWMTARSCSGEKGGHWAPRQVGVYLLPGRVGCVSS FT RVSPSFPGDGLDSGLARRGSAVSALASGLVEEPMLGPPFHPTP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14661020" FT /id="VSP_009464" FT MUTAGEN 23 FT /note="C->A: Abolishes only ubiquitin-vinylsulfone adduct FT formation." FT /evidence="ECO:0000269|PubMed:19211026" FT MUTAGEN 23 FT /note="C->S: Does not affect ability to deubiquitinate FT DEPTOR." FT /evidence="ECO:0000269|PubMed:29382726" FT MUTAGEN 26 FT /note="Y->A: Abolished ability to deubiquitinate RPTOR." FT /evidence="ECO:0000269|PubMed:35927303" FT MUTAGEN 33 FT /note="Q->R: Impairs inhibition of UBE2N/UBC13." FT /evidence="ECO:0000269|PubMed:22325355" FT MUTAGEN 37 FT /note="I->T: Impairs inhibition of UBE2N/UBC13." FT /evidence="ECO:0000269|PubMed:22325355" FT MUTAGEN 39 FT /note="Q->L: Does not affect activity in DNA repair and FT ability to inhibit UBE2N/UBC13." FT /evidence="ECO:0000269|PubMed:22325355" FT MUTAGEN 87 FT /note="P->G: Slightly improves ability to cleave FT 'K63'-linked ubiquitin." FT /evidence="ECO:0000269|PubMed:18954305" FT MUTAGEN 88 FT /note="D->A: Abolished ability to deubiquitinate DEPTOR. FT Does not affect ability to deubiquitinate RPTOR; when FT associated with A-91 and A-265." FT /evidence="ECO:0000269|PubMed:29382726, FT ECO:0000269|PubMed:35927303" FT MUTAGEN 88 FT /note="D->E: Abolishes hydrolase activity in vitro. FT Abolishes ability to inhibit RNF168; when associated with FT S-91 and A-265." FT /evidence="ECO:0000269|PubMed:12704427, FT ECO:0000269|PubMed:20725033" FT MUTAGEN 91 FT /note="C->A: Prevents RNF128 autoubiquitination, and FT stabilizes RNF128 in vivo. Abolishes both ubiquitin-binding FT and adduct formation with ubiquitin-vinylsulfone. Does not FT affect ability to deubiquitinate RPTOR; when associated FT with A-88 and A-265." FT /evidence="ECO:0000269|PubMed:12704427, FT ECO:0000269|PubMed:14661020, ECO:0000269|PubMed:18954305, FT ECO:0000269|PubMed:19211026, ECO:0000269|PubMed:19383985, FT ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, FT ECO:0000269|PubMed:35927303" FT MUTAGEN 91 FT /note="C->S: Abolishes hydrolase activity in vitro. Does FT not affect ability to inhibit RNF168. Does not affect FT ability to deubiquitinate DEPTOR. Abolishes ability to FT inhibit RNF168; when associated with E-88 and A-265." FT /evidence="ECO:0000269|PubMed:12704427, FT ECO:0000269|PubMed:14661020, ECO:0000269|PubMed:18954305, FT ECO:0000269|PubMed:19211026, ECO:0000269|PubMed:19383985, FT ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:22325355, FT ECO:0000269|PubMed:29382726" FT MUTAGEN 116 FT /note="A->T: Does not affect ability to inhibit FT UBE2N/UBC13." FT /evidence="ECO:0000269|PubMed:22325355" FT MUTAGEN 134 FT /note="T->R: Impairs inhibition of UBE2N/UBC13." FT /evidence="ECO:0000269|PubMed:22325355" FT MUTAGEN 137 FT /note="D->G: Impairs inhibition of UBE2N/UBC13." FT /evidence="ECO:0000269|PubMed:22325355" FT MUTAGEN 176 FT /note="R->L: No effect on RNF128." FT /evidence="ECO:0000269|PubMed:14661020" FT MUTAGEN 190 FT /note="F->S: Fails to inhibit ubiquitin conjugation by FT UBE2N/UBC13." FT /evidence="ECO:0000269|PubMed:22325355" FT MUTAGEN 212 FT /note="C->A: No effect on RNF128." FT /evidence="ECO:0000269|PubMed:14661020, FT ECO:0000269|PubMed:19211026" FT MUTAGEN 261 FT /note="Y->H: Impairs inhibition of UBE2N/UBC13." FT /evidence="ECO:0000269|PubMed:22325355" FT MUTAGEN 263 FT /note="P->L: Fails to inhibit ubiquitin conjugation by FT UBE2N/UBC13." FT /evidence="ECO:0000269|PubMed:22325355" FT MUTAGEN 265 FT /note="H->A: Abolishes ability to inhibit RNF168; when FT associated with A-88 and S-91. Does not affect ability to FT deubiquitinate RPTOR; when associated with A-88 and A-91." FT /evidence="ECO:0000269|PubMed:12704427, FT ECO:0000269|PubMed:20725033, ECO:0000269|PubMed:35927303" FT MUTAGEN 265 FT /note="H->R: Abolishes hydrolase activity in vitro." FT /evidence="ECO:0000269|PubMed:12704427, FT ECO:0000269|PubMed:20725033" FT CONFLICT 61 FT /note="Y -> C (in Ref. 6; AAH10368)" FT /evidence="ECO:0000305" FT CONFLICT 151 FT /note="K -> R (in Ref. 4; BAA90956)" FT /evidence="ECO:0000305" FT HELIX 24..44 FT /evidence="ECO:0007829|PDB:4LDT" FT STRAND 47..53 FT /evidence="ECO:0007829|PDB:4I6L" FT HELIX 54..60 FT /evidence="ECO:0007829|PDB:2ZFY" FT HELIX 66..75 FT /evidence="ECO:0007829|PDB:2ZFY" FT TURN 76..78 FT /evidence="ECO:0007829|PDB:2ZFY" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:2ZFY" FT STRAND 87..89 FT /evidence="ECO:0007829|PDB:4I6L" FT HELIX 91..104 FT /evidence="ECO:0007829|PDB:2ZFY" FT HELIX 108..127 FT /evidence="ECO:0007829|PDB:2ZFY" FT HELIX 132..150 FT /evidence="ECO:0007829|PDB:2ZFY" FT HELIX 155..162 FT /evidence="ECO:0007829|PDB:2ZFY" FT HELIX 165..185 FT /evidence="ECO:0007829|PDB:2ZFY" FT HELIX 187..190 FT /evidence="ECO:0007829|PDB:2ZFY" FT HELIX 191..193 FT /evidence="ECO:0007829|PDB:2ZFY" FT STRAND 194..197 FT /evidence="ECO:0007829|PDB:4DDG" FT HELIX 200..207 FT /evidence="ECO:0007829|PDB:2ZFY" FT HELIX 217..227 FT /evidence="ECO:0007829|PDB:2ZFY" FT STRAND 231..235 FT /evidence="ECO:0007829|PDB:2ZFY" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:4DDG" FT STRAND 245..250 FT /evidence="ECO:0007829|PDB:2ZFY" FT STRAND 256..262 FT /evidence="ECO:0007829|PDB:2ZFY" FT STRAND 265..270 FT /evidence="ECO:0007829|PDB:2ZFY" SQ SEQUENCE 271 AA; 31284 MW; 63188EE1DC5FD66F CRC64; MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE RLELSVLYKE YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH LEALLDDSKE LQRFKAVSAK SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE KQTSVADLLA SFNDQSTSDY LVVYLRLLTS GYLQRESKFF EHFIEGGRTV KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE GGTTNPHIFP EGSEPKVYLL YRPGHYDILY K //