UBP2_HUMAN
ID UBP2_HUMAN Reviewed; 605 AA.
AC O75604; B0YJB8; E9PPM2; Q8IUM2; Q8IW04; Q96MB9; Q9BQ21;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 2;
DE EC=3.4.19.12;
DE AltName: Full=41 kDa ubiquitin-specific protease;
DE AltName: Full=Deubiquitinating enzyme 2;
DE AltName: Full=Ubiquitin thioesterase 2;
DE AltName: Full=Ubiquitin-specific-processing protease 2;
GN Name=USP2; Synonyms=UBP41;
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 2).
RC TISSUE=Placenta;
RA Gong L., Yeh E.T.H.;
RT "Cloning and expression of the human and mouse UBP41.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Prostate cancer;
RA Rossi S., Graner E., Weinstein L.J., Loda M.;
RT "Molecular cloning and characterization of USP2b in the human prostate
RT cancer cell line LNCaP.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
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 GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lymph, and Testis;
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 [8]
RP FUNCTION, INTERACTION WITH MDM2, AND MUTAGENESIS OF HIS-549.
RX PubMed=17290220; DOI=10.1038/sj.emboj.7601567;
RA Stevenson L.F., Sparks A., Allende-Vega N., Xirodimas D.P., Lane D.P.,
RA Saville M.K.;
RT "The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting
RT Mdm2.";
RL EMBO J. 26:976-986(2007).
RN [9]
RP FUNCTION, INTERACTION WITH CCND1, AND MUTAGENESIS OF CYS-276.
RX PubMed=19917254; DOI=10.1016/j.molcel.2009.10.018;
RA Shan J., Zhao W., Gu W.;
RT "Suppression of cancer cell growth by promoting cyclin D1 degradation.";
RL Mol. Cell 36:469-476(2009).
RN [10]
RP FUNCTION, INTERACTION WITH MDM2 AND MDM4, INDUCTION, AND MUTAGENESIS OF
RP HIS-549.
RX PubMed=19838211; DOI=10.1038/onc.2009.330;
RA Allende-Vega N., Sparks A., Lane D.P., Saville M.K.;
RT "MdmX is a substrate for the deubiquitinating enzyme USP2a.";
RL Oncogene 29:432-441(2010).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=20403044; DOI=10.1111/j.1440-1827.2010.02496.x;
RA Wang S., Wu H., Liu Y., Sun J., Zhao Z., Chen Q., Guo M., Ma D., Zhang Z.;
RT "Expression of USP2-69 in mesangial cells in vivo and in vitro.";
RL Pathol. Int. 60:184-192(2010).
RN [12]
RP INTERACTION WITH KCNQ1.
RX PubMed=22024150; DOI=10.1016/j.hrthm.2011.10.026;
RA Krzystanek K., Rasmussen H.B., Grunnet M., Staub O., Olesen S.P.,
RA Abriel H., Jespersen T.;
RT "Deubiquitylating enzyme USP2 counteracts Nedd4-2-mediated downregulation
RT of KCNQ1 potassium channels.";
RL Heart Rhythm 9:440-448(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 251-605.
RG Structural genomics consortium (SGC);
RT "Covalent ubiquitin-usp2 complex.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 258-605 IN COMPLEX WITH UBIQUITIN
RP AND ZINC-BINDING, AND ACTIVITY REGULATION.
RX PubMed=16905103; DOI=10.1016/j.str.2006.06.012;
RA Renatus M., Parrado S.G., D'Arcy A., Eidhoff U., Gerhartz B., Hassiepen U.,
RA Pierrat B., Riedl R., Vinzenz D., Worpenberg S., Kroemer M.;
RT "Structural basis of ubiquitin recognition by the deubiquitinating protease
RT USP2.";
RL Structure 14:1293-1302(2006).
CC -!- FUNCTION: Hydrolase that deubiquitinates polyubiquitinated target
CC proteins such as MDM2, MDM4 and CCND1 (PubMed:17290220,
CC PubMed:19917254, PubMed:19838211). Isoform 1 and isoform 4 possess both
CC ubiquitin-specific peptidase and isopeptidase activities (By
CC similarity). Deubiquitinates MDM2 without reversing MDM2-mediated
CC p53/TP53 ubiquitination and thus indirectly promotes p53/TP53
CC degradation and limits p53 activity (PubMed:17290220, PubMed:19838211).
CC Has no deubiquitinase activity against p53/TP53 (PubMed:17290220).
CC Prevents MDM2-mediated degradation of MDM4 (PubMed:17290220). Plays a
CC role in the G1/S cell-cycle progression in normal and cancer cells
CC (PubMed:19917254). Regulates the circadian clock by modulating its
CC intrinsic circadian rhythm and its capacity to respond to external cues
CC (By similarity). Associates with clock proteins and deubiquitinates
CC core clock component PER1 but does not affect its overall stability (By
CC similarity). Regulates the nucleocytoplasmic shuttling and nuclear
CC retention of PER1 and its repressive role on the clock transcription
CC factors CLOCK and ARNTL/BMAL1 (By similarity). Plays a role in the
CC regulation of myogenic differentiation of embryonic muscle cells (By
CC similarity). {ECO:0000250|UniProtKB:O88623,
CC ECO:0000250|UniProtKB:Q5U349, ECO:0000269|PubMed:17290220,
CC ECO:0000269|PubMed:19838211, ECO:0000269|PubMed:19917254}.
CC -!- FUNCTION: [Isoform 4]: Circadian clock output effector that regulates
CC Ca(2+) absorption in the small intestine. Probably functions by
CC regulating protein levels of the membrane scaffold protein NHERF4 in a
CC rhythmic manner, and is therefore likely to control Ca(2+) membrane
CC permeability mediated by the Ca(2+) channel TRPV6 in the intestine.
CC {ECO:0000250|UniProtKB:O88623}.
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;
CC -!- ACTIVITY REGULATION: Cleavage is inhibited by ubiquitin in a dosage-
CC dependent manner. Cleavage is blocked by ubiquitin aldehyde.
CC {ECO:0000269|PubMed:16905103}.
CC -!- SUBUNIT: Homooligomer (By similarity). Found in trimeric complex with
CC MDM2 and MDM4 and USP2. Interacts with CCND1; the interaction is direct
CC and promotes its stabilization by antagonizing ubiquitin-dependent
CC degradation. Interacts (via N-terminus and C-terminus) with MDM2.
CC Interacts with MDM4. Interacts with PER1 (By similarity). Interacts
CC with KCNQ1; counteracts the NEDD4L-specific down-regulation of I(Ks)
CC and restore plasma membrane localization of KCNQ1 (PubMed:22024150).
CC Isoform 4: Interacts with PDZD3 and CLTC (By similarity).
CC {ECO:0000250|UniProtKB:O88623, ECO:0000250|UniProtKB:Q5U349,
CC ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19838211,
CC ECO:0000269|PubMed:19917254, ECO:0000269|PubMed:22024150}.
CC -!- INTERACTION:
CC O75604; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-743272, EBI-11096309;
CC O75604; P12814: ACTN1; NbExp=3; IntAct=EBI-743272, EBI-351710;
CC O75604; P35609: ACTN2; NbExp=3; IntAct=EBI-743272, EBI-77797;
CC O75604; Q08043: ACTN3; NbExp=3; IntAct=EBI-743272, EBI-2880652;
CC O75604; Q86U10: ASPG; NbExp=3; IntAct=EBI-743272, EBI-19946665;
CC O75604; Q86V38: ATN1; NbExp=3; IntAct=EBI-743272, EBI-11954292;
CC O75604; P56945: BCAR1; NbExp=3; IntAct=EBI-743272, EBI-702093;
CC O75604; Q6PI77: BHLHB9; NbExp=3; IntAct=EBI-743272, EBI-11519926;
CC O75604; Q8TD16-2: BICD2; NbExp=3; IntAct=EBI-743272, EBI-11975051;
CC O75604; Q96CA5: BIRC7; NbExp=3; IntAct=EBI-743272, EBI-517623;
CC O75604; A2RRN7: CADPS; NbExp=3; IntAct=EBI-743272, EBI-10179719;
CC O75604; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-743272, EBI-739580;
CC O75604; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-743272, EBI-11530605;
CC O75604; Q96JN2-2: CCDC136; NbExp=3; IntAct=EBI-743272, EBI-10171416;
CC O75604; Q2TAC2: CCDC57; NbExp=3; IntAct=EBI-743272, EBI-2808286;
CC O75604; A6NC98: CCDC88B; NbExp=3; IntAct=EBI-743272, EBI-347573;
CC O75604; Q96MT8-3: CEP63; NbExp=3; IntAct=EBI-743272, EBI-11522539;
CC O75604; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-743272, EBI-739624;
CC O75604; Q9BSW2: CRACR2A; NbExp=3; IntAct=EBI-743272, EBI-739773;
CC O75604; Q8N4Y2-3: CRACR2B; NbExp=3; IntAct=EBI-743272, EBI-11982645;
CC O75604; Q8WTU0: DDI1; NbExp=3; IntAct=EBI-743272, EBI-748248;
CC O75604; O75140-2: DEPDC5; NbExp=3; IntAct=EBI-743272, EBI-12366971;
CC O75604; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-743272, EBI-11988027;
CC O75604; Q8N9I9: DTX3; NbExp=3; IntAct=EBI-743272, EBI-2340258;
CC O75604; Q9H596: DUSP21; NbExp=3; IntAct=EBI-743272, EBI-7357329;
CC O75604; Q8WWB3: DYDC1; NbExp=3; IntAct=EBI-743272, EBI-740680;
CC O75604; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-743272, EBI-2349927;
CC O75604; Q9NRA8: EIF4ENIF1; NbExp=3; IntAct=EBI-743272, EBI-301024;
CC O75604; O00471: EXOC5; NbExp=3; IntAct=EBI-743272, EBI-949824;
CC O75604; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-743272, EBI-371922;
CC O75604; P57678: GEMIN4; NbExp=3; IntAct=EBI-743272, EBI-356700;
CC O75604; Q08379: GOLGA2; NbExp=6; IntAct=EBI-743272, EBI-618309;
CC O75604; Q9NYA3: GOLGA6A; NbExp=3; IntAct=EBI-743272, EBI-11163335;
CC O75604; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-743272, EBI-5916454;
CC O75604; Q14451-3: GRB7; NbExp=3; IntAct=EBI-743272, EBI-11991632;
CC O75604; Q4V328: GRIPAP1; NbExp=3; IntAct=EBI-743272, EBI-717919;
CC O75604; Q9NSC5: HOMER3; NbExp=6; IntAct=EBI-743272, EBI-748420;
CC O75604; Q9UJC3: HOOK1; NbExp=3; IntAct=EBI-743272, EBI-746704;
CC O75604; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-743272, EBI-10961706;
CC O75604; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-743272, EBI-8638439;
CC O75604; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-743272, EBI-747204;
CC O75604; Q5TA45: INTS11; NbExp=3; IntAct=EBI-743272, EBI-748258;
CC O75604; Q96N16: JAKMIP1; NbExp=3; IntAct=EBI-743272, EBI-2680803;
CC O75604; O75564-2: JRK; NbExp=3; IntAct=EBI-743272, EBI-17181882;
CC O75604; Q674X7-2: KAZN; NbExp=3; IntAct=EBI-743272, EBI-12024294;
CC O75604; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-743272, EBI-2125614;
CC O75604; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-743272, EBI-14069005;
CC O75604; P19012: KRT15; NbExp=5; IntAct=EBI-743272, EBI-739566;
CC O75604; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-743272, EBI-3044087;
CC O75604; Q15323: KRT31; NbExp=3; IntAct=EBI-743272, EBI-948001;
CC O75604; Q14525: KRT33B; NbExp=3; IntAct=EBI-743272, EBI-1049638;
CC O75604; O76011: KRT34; NbExp=3; IntAct=EBI-743272, EBI-1047093;
CC O75604; Q92764: KRT35; NbExp=3; IntAct=EBI-743272, EBI-1058674;
CC O75604; Q6A162: KRT40; NbExp=6; IntAct=EBI-743272, EBI-10171697;
CC O75604; Q9UBR4-2: LHX3; NbExp=3; IntAct=EBI-743272, EBI-12039345;
CC O75604; Q969G2: LHX4; NbExp=4; IntAct=EBI-743272, EBI-2865388;
CC O75604; Q03252: LMNB2; NbExp=3; IntAct=EBI-743272, EBI-2830427;
CC O75604; Q9BRK4: LZTS2; NbExp=6; IntAct=EBI-743272, EBI-741037;
CC O75604; Q00987: MDM2; NbExp=4; IntAct=EBI-743272, EBI-389668;
CC O75604; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-743272, EBI-10172526;
CC O75604; Q5VZ52: MORN5; NbExp=3; IntAct=EBI-743272, EBI-12835568;
CC O75604; Q13084: MRPL28; NbExp=3; IntAct=EBI-743272, EBI-723426;
CC O75604; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-743272, EBI-742948;
CC O75604; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-743272, EBI-11522433;
CC O75604; Q15742: NAB2; NbExp=3; IntAct=EBI-743272, EBI-8641936;
CC O75604; Q9GZM8: NDEL1; NbExp=6; IntAct=EBI-743272, EBI-928842;
CC O75604; I6L9F6: NEFL; NbExp=3; IntAct=EBI-743272, EBI-10178578;
CC O75604; P07196: NEFL; NbExp=3; IntAct=EBI-743272, EBI-475646;
CC O75604; O43482: OIP5; NbExp=3; IntAct=EBI-743272, EBI-536879;
CC O75604; Q96CV9: OPTN; NbExp=3; IntAct=EBI-743272, EBI-748974;
CC O75604; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-743272, EBI-14066006;
CC O75604; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-743272, EBI-79165;
CC O75604; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-743272, EBI-949255;
CC O75604; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-743272, EBI-302345;
CC O75604; Q16633: POU2AF1; NbExp=3; IntAct=EBI-743272, EBI-943588;
CC O75604; Q9GZV8: PRDM14; NbExp=3; IntAct=EBI-743272, EBI-3957793;
CC O75604; Q6MZQ0: PRR5L; NbExp=3; IntAct=EBI-743272, EBI-1567866;
CC O75604; Q15276: RABEP1; NbExp=3; IntAct=EBI-743272, EBI-447043;
CC O75604; Q8HWS3: RFX6; NbExp=3; IntAct=EBI-743272, EBI-746118;
CC O75604; Q59EK9-3: RUNDC3A; NbExp=3; IntAct=EBI-743272, EBI-11957366;
CC O75604; P60903: S100A10; NbExp=3; IntAct=EBI-743272, EBI-717048;
CC O75604; O14492-2: SH2B2; NbExp=3; IntAct=EBI-743272, EBI-19952306;
CC O75604; O60504: SORBS3; NbExp=3; IntAct=EBI-743272, EBI-741237;
CC O75604; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-743272, EBI-11959123;
CC O75604; A6NLX3: SPDYE4; NbExp=3; IntAct=EBI-743272, EBI-12047907;
CC O75604; P51692: STAT5B; NbExp=3; IntAct=EBI-743272, EBI-1186119;
CC O75604; Q86VP1: TAX1BP1; NbExp=3; IntAct=EBI-743272, EBI-529518;
CC O75604; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-743272, EBI-750487;
CC O75604; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-743272, EBI-1105213;
CC O75604; Q08117-2: TLE5; NbExp=5; IntAct=EBI-743272, EBI-11741437;
CC O75604; Q03169: TNFAIP2; NbExp=3; IntAct=EBI-743272, EBI-7954198;
CC O75604; Q13077: TRAF1; NbExp=3; IntAct=EBI-743272, EBI-359224;
CC O75604; Q12933: TRAF2; NbExp=7; IntAct=EBI-743272, EBI-355744;
CC O75604; Q9Y4K3: TRAF6; NbExp=3; IntAct=EBI-743272, EBI-359276;
CC O75604; P36406: TRIM23; NbExp=3; IntAct=EBI-743272, EBI-740098;
CC O75604; P14373: TRIM27; NbExp=6; IntAct=EBI-743272, EBI-719493;
CC O75604; Q86XT4: TRIM50; NbExp=3; IntAct=EBI-743272, EBI-9867283;
CC O75604; Q15654: TRIP6; NbExp=3; IntAct=EBI-743272, EBI-742327;
CC O75604; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-743272, EBI-739895;
CC O75604; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-743272, EBI-11975223;
CC O75604; Q9UK41-2: VPS28; NbExp=3; IntAct=EBI-743272, EBI-12146727;
CC O75604; Q8N1B4: VPS52; NbExp=6; IntAct=EBI-743272, EBI-2799833;
CC O75604; O96006: ZBED1; NbExp=3; IntAct=EBI-743272, EBI-740037;
CC O75604; Q9NZV7: ZIM2; NbExp=3; IntAct=EBI-743272, EBI-11962760;
CC O75604; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-743272, EBI-527853;
CC O75604-3; P05067: APP; NbExp=3; IntAct=EBI-10696113, EBI-77613;
CC O75604-3; P54253: ATXN1; NbExp=6; IntAct=EBI-10696113, EBI-930964;
CC O75604-3; G5E9A7: DMWD; NbExp=3; IntAct=EBI-10696113, EBI-10976677;
CC O75604-3; Q01658: DR1; NbExp=3; IntAct=EBI-10696113, EBI-750300;
CC O75604-3; Q00403: GTF2B; NbExp=3; IntAct=EBI-10696113, EBI-389564;
CC O75604-3; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-10696113, EBI-1054873;
CC O75604-3; P04792: HSPB1; NbExp=3; IntAct=EBI-10696113, EBI-352682;
CC O75604-3; O43464: HTRA2; NbExp=3; IntAct=EBI-10696113, EBI-517086;
CC O75604-3; P42858: HTT; NbExp=6; IntAct=EBI-10696113, EBI-466029;
CC O75604-3; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-10696113, EBI-1055254;
CC O75604-3; O60333-2: KIF1B; NbExp=3; IntAct=EBI-10696113, EBI-10975473;
CC O75604-3; D3DTS7: PMP22; NbExp=3; IntAct=EBI-10696113, EBI-25882629;
CC O75604-3; O60260-5: PRKN; NbExp=3; IntAct=EBI-10696113, EBI-21251460;
CC O75604-3; P60891: PRPS1; NbExp=3; IntAct=EBI-10696113, EBI-749195;
CC O75604-3; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-10696113, EBI-396669;
CC O75604-3; Q7Z333: SETX; NbExp=3; IntAct=EBI-10696113, EBI-1220123;
CC O75604-3; P37840: SNCA; NbExp=3; IntAct=EBI-10696113, EBI-985879;
CC O75604-3; P00441: SOD1; NbExp=3; IntAct=EBI-10696113, EBI-990792;
CC O75604-3; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-10696113, EBI-5235340;
CC O75604-3; Q13148: TARDBP; NbExp=6; IntAct=EBI-10696113, EBI-372899;
CC O75604-3; O76024: WFS1; NbExp=3; IntAct=EBI-10696113, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O88623}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:O88623}.
CC Note=Localizes in the spermatid head in late-elongating spermatids in
CC the thin area between the outer acrosomal membrane and the plasma
CC membrane. {ECO:0000250|UniProtKB:Q5U349}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Nucleus
CC {ECO:0000250|UniProtKB:Q5U349}. Membrane
CC {ECO:0000250|UniProtKB:O88623}; Peripheral membrane protein
CC {ECO:0000305}. Cytoplasm {ECO:0000250|UniProtKB:O88623}.
CC Note=Predominantly expressed at membranes.
CC {ECO:0000250|UniProtKB:O88623}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=USP2a, USP2-69;
CC IsoId=O75604-1; Sequence=Displayed;
CC Name=2; Synonyms=USP2b;
CC IsoId=O75604-2; Sequence=VSP_005256, VSP_005257;
CC Name=3;
CC IsoId=O75604-3; Sequence=VSP_039559;
CC Name=4;
CC IsoId=O75604-4; Sequence=VSP_039560;
CC -!- TISSUE SPECIFICITY: Expressed in mesangial cells of the kidney and in
CC different types of glomerulonephritides (at protein level).
CC {ECO:0000269|PubMed:20403044}.
CC -!- INDUCTION: Down-regulated by cisplatin (at protein level).
CC {ECO:0000269|PubMed:19838211}.
CC -!- DOMAIN: The different N-terminus extensions of isoform 1 and isoform 4
CC determine their respective subcellular localization and differentiel
CC effect on myoblast fusion and accumulation of muscle-specific proteins.
CC The different N-terminus extensions of isoform 1 and isoform 4 are not
CC essential for their catalytic activity. {ECO:0000250|UniProtKB:Q5U349}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP2 subfamily.
CC {ECO:0000305}.
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DR EMBL; AF079564; AAC28392.1; -; mRNA.
DR EMBL; AF440755; AAN65363.1; -; mRNA.
DR EMBL; AK057225; BAB71388.1; -; mRNA.
DR EMBL; AK292255; BAF84944.1; -; mRNA.
DR EMBL; EF445044; ACA06096.1; -; Genomic_DNA.
DR EMBL; EF445044; ACA06097.1; -; Genomic_DNA.
DR EMBL; AP003396; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67484.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67485.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67486.1; -; Genomic_DNA.
DR EMBL; BC002854; AAH02854.1; -; mRNA.
DR EMBL; BC002955; AAH02955.1; -; mRNA.
DR EMBL; BC041366; AAH41366.1; -; mRNA.
DR CCDS; CCDS58189.1; -. [O75604-3]
DR CCDS; CCDS8422.1; -. [O75604-1]
DR CCDS; CCDS8423.1; -. [O75604-4]
DR RefSeq; NP_001230688.1; NM_001243759.1. [O75604-3]
DR RefSeq; NP_004196.4; NM_004205.4. [O75604-1]
DR RefSeq; NP_741994.1; NM_171997.2. [O75604-4]
DR RefSeq; XP_005271778.1; XM_005271721.4. [O75604-1]
DR RefSeq; XP_005271779.1; XM_005271722.2. [O75604-1]
DR PDB; 2HD5; X-ray; 1.85 A; A=258-605.
DR PDB; 2IBI; X-ray; 2.20 A; A=251-605.
DR PDB; 3NHE; X-ray; 1.26 A; A=258-605.
DR PDB; 3V6C; X-ray; 1.70 A; A=258-605.
DR PDB; 3V6E; X-ray; 2.10 A; A=258-605.
DR PDB; 5XU8; X-ray; 1.81 A; A=258-605.
DR PDB; 5XVE; X-ray; 1.24 A; A=258-605.
DR PDB; 6DGF; X-ray; 2.34 A; A=250-605.
DR PDBsum; 2HD5; -.
DR PDBsum; 2IBI; -.
DR PDBsum; 3NHE; -.
DR PDBsum; 3V6C; -.
DR PDBsum; 3V6E; -.
DR PDBsum; 5XU8; -.
DR PDBsum; 5XVE; -.
DR PDBsum; 6DGF; -.
DR AlphaFoldDB; O75604; -.
DR SMR; O75604; -.
DR BioGRID; 114553; 215.
DR CORUM; O75604; -.
DR DIP; DIP-29134N; -.
DR IntAct; O75604; 137.
DR MINT; O75604; -.
DR STRING; 9606.ENSP00000260187; -.
DR BindingDB; O75604; -.
DR ChEMBL; CHEMBL1293227; -.
DR MEROPS; C19.013; -.
DR MoonDB; O75604; Predicted.
DR GlyGen; O75604; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75604; -.
DR PhosphoSitePlus; O75604; -.
DR BioMuta; USP2; -.
DR MassIVE; O75604; -.
DR MaxQB; O75604; -.
DR PaxDb; O75604; -.
DR PeptideAtlas; O75604; -.
DR PRIDE; O75604; -.
DR ProteomicsDB; 22761; -.
DR ProteomicsDB; 50112; -. [O75604-1]
DR ProteomicsDB; 50113; -. [O75604-2]
DR ProteomicsDB; 50114; -. [O75604-3]
DR ProteomicsDB; 50115; -. [O75604-4]
DR Antibodypedia; 1707; 431 antibodies from 33 providers.
DR DNASU; 9099; -.
DR Ensembl; ENST00000260187.7; ENSP00000260187.2; ENSG00000036672.16. [O75604-1]
DR Ensembl; ENST00000455332.6; ENSP00000407842.2; ENSG00000036672.16. [O75604-3]
DR Ensembl; ENST00000525735.1; ENSP00000436952.1; ENSG00000036672.16. [O75604-4]
DR GeneID; 9099; -.
DR KEGG; hsa:9099; -.
DR MANE-Select; ENST00000260187.7; ENSP00000260187.2; NM_004205.5; NP_004196.4.
DR UCSC; uc001pwl.5; human. [O75604-1]
DR CTD; 9099; -.
DR DisGeNET; 9099; -.
DR GeneCards; USP2; -.
DR HGNC; HGNC:12618; USP2.
DR HPA; ENSG00000036672; Tissue enhanced (skeletal muscle, testis).
DR MIM; 604725; gene.
DR neXtProt; NX_O75604; -.
DR OpenTargets; ENSG00000036672; -.
DR PharmGKB; PA37244; -.
DR VEuPathDB; HostDB:ENSG00000036672; -.
DR eggNOG; KOG1868; Eukaryota.
DR GeneTree; ENSGT00940000161289; -.
DR HOGENOM; CLU_008279_1_2_1; -.
DR InParanoid; O75604; -.
DR OMA; KYWVKYL; -.
DR OrthoDB; 1283205at2759; -.
DR PhylomeDB; O75604; -.
DR TreeFam; TF106277; -.
DR PathwayCommons; O75604; -.
DR Reactome; R-HSA-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-HSA-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR SignaLink; O75604; -.
DR BioGRID-ORCS; 9099; 13 hits in 1125 CRISPR screens.
DR ChiTaRS; USP2; human.
DR EvolutionaryTrace; O75604; -.
DR GeneWiki; USP2; -.
DR GenomeRNAi; 9099; -.
DR Pharos; O75604; Tbio.
DR PRO; PR:O75604; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O75604; protein.
DR Bgee; ENSG00000036672; Expressed in hindlimb stylopod muscle and 154 other tissues.
DR ExpressionAtlas; O75604; baseline and differential.
DR Genevisible; O75604; HS.
DR GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030332; F:cyclin binding; IPI:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:FlyBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0048512; P:circadian behavior; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0045475; P:locomotor rhythm; ISS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Biological rhythms; Cell cycle;
KW Cytoplasm; Hydrolase; Membrane; Metal-binding; Myogenesis; Nucleus;
KW Protease; Reference proteome; Thiol protease; Ubl conjugation pathway;
KW Zinc.
FT CHAIN 1..605
FT /note="Ubiquitin carboxyl-terminal hydrolase 2"
FT /id="PRO_0000080616"
FT DOMAIN 267..599
FT /note="USP"
FT REGION 1..200
FT /note="Necessary for interaction with MDM4"
FT /evidence="ECO:0000269|PubMed:19838211"
FT REGION 71..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..503
FT /note="Necessary for interaction with MDM4"
FT /evidence="ECO:0000269|PubMed:19838211"
FT COMPBIAS 244..264
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 276
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 557
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 425
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16905103"
FT BINDING 428
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16905103"
FT BINDING 476
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16905103"
FT BINDING 479
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16905103"
FT VAR_SEQ 1..258
FT /note="MSQLSSTLKRYTESARYTDAHYAKSGYGAYTPSSYGANLAASLLEKEKLGFK
FT PVPTSSFLTRPRTYGPSSLLDYDRGRPLLRPDITGGGKRAESQTRGTERPLGSGLSGGS
FT GFPYGVTNNCLSYLPINAYDQGVTLTQKLDSQSDLARDFSSLRTSDSYRIDPRNLGRSP
FT MLARTRKELCTLQGLYQTASCPEYLVDYLENYGRKGSASQVPSQAPPSRVPEIISPTYR
FT PIGRYTLWETGKGQAPGPSRSSSPGRDGM -> MLVPGSTRPYSKKRQ (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039559"
FT VAR_SEQ 1..258
FT /note="MSQLSSTLKRYTESARYTDAHYAKSGYGAYTPSSYGANLAASLLEKEKLGFK
FT PVPTSSFLTRPRTYGPSSLLDYDRGRPLLRPDITGGGKRAESQTRGTERPLGSGLSGGS
FT GFPYGVTNNCLSYLPINAYDQGVTLTQKLDSQSDLARDFSSLRTSDSYRIDPRNLGRSP
FT MLARTRKELCTLQGLYQTASCPEYLVDYLENYGRKGSASQVPSQAPPSRVPEIISPTYR
FT PIGRYTLWETGKGQAPGPSRSSSPGRDGM -> MRTSYTVTLPEDPPAAPFPALAKELR
FT PRSPLSPSLLLSTFVGLLLNKAK (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2"
FT /id="VSP_039560"
FT VAR_SEQ 1..252
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_005256"
FT VAR_SEQ 253..258
FT /note="PGRDGM -> MLNKAK (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_005257"
FT VARIANT 174
FT /note="R -> Q (in dbSNP:rs33929148)"
FT /id="VAR_051519"
FT VARIANT 383
FT /note="N -> S (in dbSNP:rs45533837)"
FT /id="VAR_051520"
FT MUTAGEN 276
FT /note="C->A: Loss of enzymatic activity. Increases the
FT steady-state level of CCND1."
FT /evidence="ECO:0000269|PubMed:19917254"
FT MUTAGEN 549
FT /note="H->A: Loss of enzymatic activity. Increases the
FT steady-state level of MDM2 and MDM4 that leads to
FT attenuation of MDM2-mediated degradation of p53/TP53 and
FT MDM4. Increases the level of p53/TP53 and MDM4 ubiquitin
FT conjugates."
FT /evidence="ECO:0000269|PubMed:17290220,
FT ECO:0000269|PubMed:19838211"
FT CONFLICT 421
FT /note="S -> G (in Ref. 3; BAB71388)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="H -> R (in Ref. 3; BAB71388)"
FT /evidence="ECO:0000305"
FT CONFLICT 594
FT /note="L -> H (in Ref. 1; AAC28392)"
FT /evidence="ECO:0000305"
FT CONFLICT 602..605
FT /note="PSRM -> TSPI (in Ref. 1; AAC28392)"
FT /evidence="ECO:0000305"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:3V6E"
FT HELIX 276..286
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 289..296
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 299..302
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 312..325
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 337..346
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:3NHE"
FT HELIX 358..373
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 392..404
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 410..415
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 417..425
FT /evidence="ECO:0007829|PDB:5XVE"
FT TURN 426..428
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 431..443
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 450..454
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 455..463
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:5XVE"
FT TURN 477..480
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 485..493
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 496..502
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 505..508
FT /evidence="ECO:0007829|PDB:6DGF"
FT STRAND 509..511
FT /evidence="ECO:0007829|PDB:5XU8"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:6DGF"
FT HELIX 529..531
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 532..534
FT /evidence="ECO:0007829|PDB:5XU8"
FT STRAND 540..551
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:3V6C"
FT STRAND 556..563
FT /evidence="ECO:0007829|PDB:5XVE"
FT TURN 565..567
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 570..574
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 577..581
FT /evidence="ECO:0007829|PDB:5XVE"
FT HELIX 583..585
FT /evidence="ECO:0007829|PDB:5XVE"
FT STRAND 591..598
FT /evidence="ECO:0007829|PDB:5XVE"
FT CONFLICT O75604-3:10
FT /note="Y -> S (in Ref. 7; AAH41366)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 605 AA; 68072 MW; AFF4DA9344D21812 CRC64;
MSQLSSTLKR YTESARYTDA HYAKSGYGAY TPSSYGANLA ASLLEKEKLG FKPVPTSSFL
TRPRTYGPSS LLDYDRGRPL LRPDITGGGK RAESQTRGTE RPLGSGLSGG SGFPYGVTNN
CLSYLPINAY DQGVTLTQKL DSQSDLARDF SSLRTSDSYR IDPRNLGRSP MLARTRKELC
TLQGLYQTAS CPEYLVDYLE NYGRKGSASQ VPSQAPPSRV PEIISPTYRP IGRYTLWETG
KGQAPGPSRS SSPGRDGMNS KSAQGLAGLR NLGNTCFMNS ILQCLSNTRE LRDYCLQRLY
MRDLHHGSNA HTALVEEFAK LIQTIWTSSP NDVVSPSEFK TQIQRYAPRF VGYNQQDAQE
FLRFLLDGLH NEVNRVTLRP KSNPENLDHL PDDEKGRQMW RKYLEREDSR IGDLFVGQLK
SSLTCTDCGY CSTVFDPFWD LSLPIAKRGY PEVTLMDCMR LFTKEDVLDG DEKPTCCRCR
GRKRCIKKFS IQRFPKILVL HLKRFSESRI RTSKLTTFVN FPLRDLDLRE FASENTNHAV
YNLYAVSNHS GTTMGGHYTA YCRSPGTGEW HTFNDSSVTP MSSSQVRTSD AYLLFYELAS
PPSRM
