ID TRI25_HUMAN Reviewed; 630 AA. AC Q14258; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 2. DT 27-MAR-2024, entry version 226. DE RecName: Full=E3 ubiquitin/ISG15 ligase TRIM25; DE EC=6.3.2.n3 {ECO:0000269|PubMed:16352599}; DE AltName: Full=Estrogen-responsive finger protein {ECO:0000303|PubMed:8248217}; DE AltName: Full=RING finger protein 147; DE AltName: Full=RING-type E3 ubiquitin transferase; DE EC=2.3.2.27 {ECO:0000269|PubMed:17392790, ECO:0000269|PubMed:27425606, ECO:0000269|PubMed:28202764, ECO:0000269|PubMed:36067236}; DE AltName: Full=RING-type E3 ubiquitin transferase TRIM25 {ECO:0000305}; DE AltName: Full=Tripartite motif-containing protein 25; DE AltName: Full=Ubiquitin/ISG15-conjugating enzyme TRIM25; DE AltName: Full=Zinc finger protein 147; GN Name=TRIM25; GN Synonyms=EFP {ECO:0000303|PubMed:8248217}, RNF147, ZNF147; 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], AND VARIANT LEU-358. RC TISSUE=Placenta; RX PubMed=8248217; DOI=10.1073/pnas.90.23.11117; RA Inoue S., Orimo A., Hosoi T., Kondo S., Toyoshima H., Kondo T., Ikegami A., RA Ouchi Y., Orimo H., Muramatsu M.; RT "Genomic binding-site cloning reveals an estrogen-responsive gene that RT encodes a RING finger protein."; RL Proc. Natl. Acad. Sci. U.S.A. 90:11117-11121(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-358. RC TISSUE=Lymph; 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 [4] RP TISSUE SPECIFICITY. RX PubMed=15130519; DOI=10.1016/j.mce.2003.12.008; RA Shimada N., Suzuki T., Inoue S., Kato K., Imatani A., Sekine H., Ohara S., RA Shimosegawa T., Sasano H.; RT "Systemic distribution of estrogen-responsive finger protein (Efp) in human RT tissues."; RL Mol. Cell. Endocrinol. 218:147-153(2004). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [6] RP INDUCTION, AND FUNCTION. RX PubMed=17069755; DOI=10.1016/j.bbrc.2006.10.061; RA Nakasato N., Ikeda K., Urano T., Horie-Inoue K., Takeda S., Inoue S.; RT "A ubiquitin E3 ligase Efp is up-regulated by interferons and conjugated RT with ISG15."; RL Biochem. Biophys. Res. Commun. 351:540-546(2006). RN [7] RP FUNCTION AS A ISG15 E3 LIGASE, CATALYTIC ACTIVITY, AND INDUCTION. RX PubMed=16352599; DOI=10.1074/jbc.m510787200; RA Zou W., Zhang D.-E.; RT "The interferon-inducible ubiquitin-protein isopeptide ligase (E3) EFP also RT functions as an ISG15 E3 ligase."; RL J. Biol. Chem. 281:3989-3994(2006). RN [8] RP ISGYLATION AT LYS-117, MUTAGENESIS OF LYS-21; LYS-65; LYS-112 AND LYS-117, RP AND AUTOISGYLATION. RX PubMed=17222803; DOI=10.1016/j.bbrc.2006.12.210; RA Zou W., Wang J., Zhang D.-E.; RT "Negative regulation of ISG15 E3 ligase EFP through its autoISGylation."; RL Biochem. Biophys. Res. Commun. 354:321-327(2007). RN [9] RP FUNCTION AS AN UBIQUITIN LIGASE, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, RP AND INTERACTION WITH RIGI. RX PubMed=17392790; DOI=10.1038/nature05732; RA Gack M.U., Shin Y.C., Joo C.H., Urano T., Liang C., Sun L., Takeuchi O., RA Akira S., Chen Z., Inoue S., Jung J.U.; RT "TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated RT antiviral activity."; RL Nature 446:916-920(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, 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 [11] RP INTERACTION WITH INFLUENZA VIRUS PROTEIN NS1 (MICROBIAL INFECTION). RX PubMed=19454348; DOI=10.1016/j.chom.2009.04.006; RA Gack M.U., Albrecht R.A., Urano T., Inn K.-S., Huang I.-C., Carnero E., RA Farzan M., Inoue S., Jung J.U., Garcia-Sastre A.; RT "Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade RT recognition by the host viral RNA sensor RIG-I."; RL Cell Host Microbe 5:439-449(2009). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-273 AND LYS-567, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [15] RP FUNCTION, INTERACTION WITH ZFHX3, AND TISSUE SPECIFICITY. RX PubMed=22452784; DOI=10.1042/bj20111890; RA Dong X.Y., Fu X., Fan S., Guo P., Su D., Dong J.T.; RT "Oestrogen causes ATBF1 protein degradation through the oestrogen- RT responsive E3 ubiquitin ligase EFP."; RL Biochem. J. 444:581-590(2012). RN [16] RP INTERACTION WITH YWHAE. RX PubMed=22607805; DOI=10.1016/j.chom.2012.04.006; RA Liu H.M., Loo Y.M., Horner S.M., Zornetzer G.A., Katze M.G., Gale M. Jr.; RT "The mitochondrial targeting chaperone 14-3-3epsilon regulates a RIG-I RT translocon that mediates membrane association and innate antiviral RT immunity."; RL Cell Host Microbe 11:528-537(2012). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-91 AND SER-100, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP FUNCTION, INTERACTION WITH RIGI, AND SUBCELLULAR LOCATION. RX PubMed=23950712; DOI=10.1371/journal.ppat.1003533; RA Oshiumi H., Miyashita M., Matsumoto M., Seya T.; RT "A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RT RIG-I repressor domain in human antiviral innate immune responses."; RL PLoS Pathog. 9:E1003533-E1003533(2013). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-278, AND IDENTIFICATION BY RP 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 [20] RP INTERACTION WITH SFTSV NSS (MICROBIAL INFECTION). RX PubMed=24478431; DOI=10.1128/jvi.03021-13; RA Santiago F.W., Covaleda L.M., Sanchez-Aparicio M.T., Silvas J.A., RA Diaz-Vizarreta A.C., Patel J.R., Popov V., Yu X.J., Garcia-Sastre A., RA Aguilar P.V.; RT "Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic RT structures correlates with the inhibition of type I interferon responses."; RL J. Virol. 88:4572-4585(2014). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-50 AND CYS-53. RX PubMed=28202764; DOI=10.1128/jvi.00088-17; RA Zheng X., Wang X., Tu F., Wang Q., Fan Z., Gao G.; RT "TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral RT Protein."; RL J. Virol. 91:0-0(2017). RN [22] RP FUNCTION, AND SUBUNIT. RX PubMed=28060952; DOI=10.1371/journal.ppat.1006145; RA Li M.M., Lau Z., Cheung P., Aguilar E.G., Schneider W.M., Bozzacco L., RA Molina H., Buehler E., Takaoka A., Rice C.M., Felsenfeld D.P., RA MacDonald M.R.; RT "TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein RT (ZAP)."; RL PLoS Pathog. 13:e1006145-e1006145(2017). RN [23] RP FUNCTION. RX PubMed=30193849; DOI=10.1016/j.immuni.2018.08.014; RA Lian H., Zang R., Wei J., Ye W., Hu M.M., Chen Y.D., Zhang X.N., Guo Y., RA Lei C.Q., Yang Q., Luo W.W., Li S., Shu H.B.; RT "The zinc-finger protein ZCCHC3 binds RNA and facilitates viral RNA sensing RT and activation of the RIG-I-like receptors."; RL Immunity 49:438-448(2018). RN [24] RP INTERACTION WITH HRSV NON-STRUCTURAL PROTEIN 1 (MICROBIAL INFECTION). RX PubMed=30558248; DOI=10.3390/v10120716; RA Ban J., Lee N.R., Lee N.J., Lee J.K., Quan F.S., Inn K.S.; RT "Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I RT Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling."; RL Viruses 10:0-0(2018). RN [25] RP FUNCTION, SUBUNIT, AUTOUBIQUITINATION, AND INTERACTION WITH YWHAZ AND RP EPSTEIN-BARR VIRUS PROTEIN BPLF1 (MICROBIAL INFECTION). RX PubMed=29357390; DOI=10.1371/journal.ppat.1006852; RA Gupta S., Ylae-Anttila P., Callegari S., Tsai M.H., Delecluse H.J., RA Masucci M.G.; RT "Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 RT autoubiquitination and functional inactivation of the RIG-I signalosome."; RL PLoS Pathog. 14:e1006852-e1006852(2018). RN [26] RP FUNCTION, SUBUNIT, AUTOUBIQUITINATION, AND INTERACTION WITH YWHAZ AND RP EPSTEIN-BARR VIRUS PROTEIN BPLF1 (MICROBIAL INFECTION). RX PubMed=31710640; DOI=10.1371/journal.ppat.1008146; RA Gupta S., Ylae-Anttila P., Sandalova T., Sun R., Achour A., Masucci M.G.; RT "14-3-3 scaffold proteins mediate the inactivation of trim25 and inhibition RT of the type I interferon response by herpesvirus deconjugases."; RL PLoS Pathog. 15:e1008146-e1008146(2019). RN [27] RP INTERACTION WITH NLRP12. RX PubMed=30902577; DOI=10.1016/j.chom.2019.02.013; RA Chen S.T., Chen L., Lin D.S., Chen S.Y., Tsao Y.P., Guo H., Li F.J., RA Tseng W.T., Tam J.W., Chao C.W., Brickey W.J., Dzhagalov I., Song M.J., RA Kang H.R., Jung J.U., Ting J.P.; RT "NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with RT TRIM25."; RL Cell Host Microbe 0:0-0(2019). RN [28] RP FUNCTION, AND INTERACTION WITH JC VIRUS SMALL T ANTIGEN (MICROBIAL RP INFECTION). RX PubMed=33849980; DOI=10.1128/mbio.00620-21; RA Chiang C., Dvorkin S., Chiang J.J., Potter R.B., Gack M.U.; RT "The Small t Antigen of JC Virus Antagonizes RIG-I-Mediated Innate Immunity RT by Inhibiting TRIM25's RNA Binding Ability."; RL MBio 12:0-0(2021). RN [29] RP INTERACTION WITH RTN3. RX PubMed=34313226; DOI=10.7554/elife.68958; RA Yang Z., Wang J., He B., Zhang X., Li X., Kuang E.; RT "RTN3 inhibits RIG-I-mediated antiviral responses by impairing TRIM25- RT mediated K63-linked polyubiquitination."; RL Elife 10:0-0(2021). RN [30] RP FUNCTION, MUTAGENESIS OF ARG-54, AND CATALYTIC ACTIVITY. RX PubMed=36067236; DOI=10.1371/journal.ppat.1010743; RA Yang E., Huang S., Jami-Alahmadi Y., McInerney G.M., Wohlschlegel J.A., RA Li M.M.H.; RT "Elucidation of TRIM25 ubiquitination targets involved in diverse cellular RT and antiviral processes."; RL PLoS Pathog. 18:e1010743-e1010743(2022). RN [31] RP FUNCTION, AND INTERACTION WITH HUMAN METAPNEUMOVIRUS M2-2 (MICROBIAL RP INFECTION). RX PubMed=36045682; DOI=10.3389/fimmu.2022.970750; RA Tanaka Y., Morita N., Kitagawa Y., Gotoh B., Komatsu T.; RT "Human metapneumovirus M2-2 protein inhibits RIG-I signaling by preventing RT TRIM25-mediated RIG-I ubiquitination."; RL Front. Immunol. 13:970750-970750(2022). RN [32] {ECO:0007744|PDB:5EYA} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-83 IN COMPLEX WITH ZN(2+), RP ACTIVITY REGULATION, SUBUNIT, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-65 RP AND ASN-71. RX PubMed=27425606; DOI=10.1016/j.celrep.2016.06.070; RA Sanchez J.G., Chiang J.J., Sparrer K.M.J., Alam S.L., Chi M., RA Roganowicz M.D., Sankaran B., Gack M.U., Pornillos O.; RT "Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway."; RL Cell Rep. 16:1315-1325(2016). RN [33] {ECO:0007744|PDB:5FER} RP X-RAY CRYSTALLOGRAPHY (2.34 ANGSTROMS) OF 1-82 IN COMPLEX WITH ZN(2+), AND RP SUBUNIT. RX PubMed=27154206; DOI=10.15252/embj.201593741; RA Koliopoulos M.G., Esposito D., Christodoulou E., Taylor I.A., Rittinger K.; RT "Functional role of TRIM E3 ligase oligomerization and regulation of RT catalytic activity."; RL EMBO J. 35:1204-1218(2016). RN [34] RP VARIANT [LARGE SCALE ANALYSIS] LEU-358, AND IDENTIFICATION BY MASS RP 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). CC -!- FUNCTION: Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase CC (PubMed:16352599). Involved in innate immune defense against viruses by CC mediating ubiquitination of RIGI and IFIH1 (PubMed:17392790, CC PubMed:30193849, PubMed:33849980, PubMed:29357390, PubMed:31710640, CC PubMed:36045682). Mediates 'Lys-63'-linked polyubiquitination of the CC RIGI N-terminal CARD-like region and may play a role in signal CC transduction that leads to the production of interferons in response to CC viral infection (PubMed:17392790, PubMed:23950712). Mediates 'Lys-63'- CC linked polyubiquitination of IFIH1 (PubMed:30193849). Promotes CC ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the CC regulation of a large spectrum signaling pathway (PubMed:16352599, CC PubMed:17069755). Mediates estrogen action in various target organs CC (PubMed:22452784). Mediates the ubiquitination and subsequent CC proteasomal degradation of ZFHX3 (PubMed:22452784). Plays a role in CC promoting the restart of stalled replication forks via interaction with CC the KHDC3L-OOEP scaffold and subsequent ubiquitination of BLM, CC resulting in the recruitment and retainment of BLM at DNA replication CC forks (By similarity). Plays an essential role in the antiviral CC activity of ZAP/ZC3HAV1; an antiviral protein which inhibits the CC replication of certain viruses. Mechanistically, mediates 'Lys-63'- CC linked polyubiquitination of ZAP/ZC3HAV1 that is required for its CC optimal binding to target mRNA (PubMed:28202764, PubMed:28060952). CC Mediates also the ubiquitination of various substrates implicated in CC stress granule formation, nonsense-mediated mRNA decay, nucleoside CC synthesis and mRNA translation and stability (PubMed:36067236). CC {ECO:0000250|UniProtKB:Q61510, ECO:0000269|PubMed:16352599, CC ECO:0000269|PubMed:17069755, ECO:0000269|PubMed:17392790, CC ECO:0000269|PubMed:22452784, ECO:0000269|PubMed:23950712, CC ECO:0000269|PubMed:29357390, ECO:0000269|PubMed:30193849, CC ECO:0000269|PubMed:31710640, ECO:0000269|PubMed:33849980, CC ECO:0000269|PubMed:36045682, ECO:0000269|PubMed:36067236}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:17392790, CC ECO:0000269|PubMed:27425606, ECO:0000269|PubMed:28202764, CC ECO:0000269|PubMed:36067236}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + [ISG15] + [protein]-lysine = AMP + diphosphate + CC [protein]-N-ISGyllysine.; EC=6.3.2.n3; CC Evidence={ECO:0000269|PubMed:16352599}; CC -!- ACTIVITY REGULATION: RING domain dimerization is required for CC catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, CC and antiviral activity. {ECO:0000269|PubMed:27425606}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Forms homodimers (PubMed:27425606, PubMed:27154206, CC PubMed:29357390, PubMed:31710640). Interacts (via SPRY domain) with CC RIGI (via CARD domain). Interacts with ZFHX3. Interacts with NLRP12; CC this interaction reduces the E3 ubiquitin ligase TRIM25-mediated 'Lys- CC 63'-linked RIGI activation. Interacts with the KHDC3L/FILIA-OOEP/FLOPED CC scaffold complex and BLM at DNA replication forks (By similarity). CC Interacts with RTN3; this interaction prevents RIGI ubiquitination CC (PubMed:34313226). Interacts with YWHAE (PubMed:22607805). CC {ECO:0000250|UniProtKB:Q61510, ECO:0000269|PubMed:17392790, CC ECO:0000269|PubMed:22452784, ECO:0000269|PubMed:22607805, CC ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:27425606, CC ECO:0000269|PubMed:29357390, ECO:0000269|PubMed:30902577, CC ECO:0000269|PubMed:31710640, ECO:0000269|PubMed:34313226}. CC -!- SUBUNIT: (Microbial infection) Interacts (via coiled coil) with CC influenza A virus NS1 protein; this interaction specifically inhibits CC TRIM25 multimerization and TRIM25-mediated RIGI CARD ubiquitination, CC thereby suppressing RIGI signal transduction. CC {ECO:0000269|PubMed:19454348}. CC -!- SUBUNIT: (Microbial infection) Interacts (via SPRY domain) with human CC respiratory syncytial virus (HRSV) non-structural protein 1; this CC interaction suppresses RIGI ubiquitination and results in decreased CC interaction between RIGI and MAVS. {ECO:0000269|PubMed:30558248}. CC -!- SUBUNIT: (Microbial infection) Interacts with JC virus small t antigen; CC this interaction suppresses RIGI ubiquitination thereby suppressing CC RIGI signal transduction. {ECO:0000269|PubMed:33849980}. CC -!- SUBUNIT: (Microbial infection) Interacts with Severe fever with CC thrombocytopenia virus (SFTSV) NSs; this interaction this interaction CC sequesters TRIM25 in NSs-induced cytoplasmic inclusion bodies thereby CC inhibiting the IFN responses. {ECO:0000269|PubMed:24478431}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus CC protein BPLF1 and YWHAZ; leading to inhibition of the type-I IFN CC response. {ECO:0000269|PubMed:29357390, ECO:0000269|PubMed:31710640}. CC -!- SUBUNIT: (Microbial infection) Interacts with human metapneumovirus CC protein M2-2; this interaction suppresses RIGI ubiquitination thereby CC suppressing RIGI signal transduction. {ECO:0000269|PubMed:36045682}. CC -!- INTERACTION: CC Q14258; Q13283: G3BP1; NbExp=2; IntAct=EBI-2341129, EBI-1047359; CC Q14258; O95786: RIGI; NbExp=9; IntAct=EBI-2341129, EBI-995350; CC Q14258; K9N4V7: N; Xeno; NbExp=2; IntAct=EBI-2341129, EBI-25592177; CC Q14258; P0DTC9: N; Xeno; NbExp=13; IntAct=EBI-2341129, EBI-25475856; CC Q14258; P03496: NS; Xeno; NbExp=3; IntAct=EBI-2341129, EBI-2547442; CC Q14258; A0A0B5AC19: NSS; Xeno; NbExp=6; IntAct=EBI-2341129, EBI-9687469; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17392790}. CC Cytoplasm, Stress granule {ECO:0000269|PubMed:23950712}. Nucleus CC {ECO:0000250|UniProtKB:Q61510}. CC -!- TISSUE SPECIFICITY: Expressed in breast tumors (at protein level). CC Ubiquitous. {ECO:0000269|PubMed:15130519, ECO:0000269|PubMed:22452784}. CC -!- INDUCTION: By interferons. {ECO:0000269|PubMed:16352599, CC ECO:0000269|PubMed:17069755}. CC -!- DOMAIN: The RING-type zinc finger is important for ISG15 E3 ligase CC activity and autoISGylation. AutoISGylation negatively regulates ISG15 CC E3 ligase activity. CC -!- DOMAIN: The C-terminal B30.2/SPRY domain interacts with the first N- CC terminal CARD domain of RIGI. CC -!- PTM: Auto-ISGylated. {ECO:0000269|PubMed:17222803}. CC -!- PTM: (Microbial infection) Autoubiquitinated; promoted by Epstein-Barr CC virus protein BPLF1. {ECO:0000269|PubMed:29357390, CC ECO:0000269|PubMed:31710640}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=TRIM25 entry; CC URL="https://en.wikipedia.org/wiki/TRIM25"; 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; D21205; BAA04747.1; -; mRNA. DR EMBL; AC015912; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC016924; AAH16924.1; -; mRNA. DR EMBL; BC042541; AAH42541.1; -; mRNA. DR CCDS; CCDS11591.1; -. DR PIR; A49656; A49656. DR RefSeq; NP_005073.2; NM_005082.4. DR PDB; 4CFG; X-ray; 2.80 A; A/B=1-630. DR PDB; 4LTB; X-ray; 2.59 A; A/B=189-379. DR PDB; 5EYA; X-ray; 2.40 A; F/G=1-83. DR PDB; 5FER; X-ray; 2.34 A; A/D=1-82. DR PDB; 5NT1; X-ray; 2.82 A; A/E/I=190-379. DR PDB; 5NT2; X-ray; 4.26 A; A/I/N/V=190-379. DR PDB; 6FLM; X-ray; 2.01 A; A/B/C=435-630. DR PDB; 6FLN; X-ray; 3.60 A; A/B/E=189-630. DR PDBsum; 4CFG; -. DR PDBsum; 4LTB; -. DR PDBsum; 5EYA; -. DR PDBsum; 5FER; -. DR PDBsum; 5NT1; -. DR PDBsum; 5NT2; -. DR PDBsum; 6FLM; -. DR PDBsum; 6FLN; -. DR AlphaFoldDB; Q14258; -. DR BMRB; Q14258; -. DR SASBDB; Q14258; -. DR SMR; Q14258; -. DR BioGRID; 113500; 2510. DR CORUM; Q14258; -. DR IntAct; Q14258; 64. DR MINT; Q14258; -. DR STRING; 9606.ENSP00000323889; -. DR GlyGen; Q14258; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q14258; -. DR PhosphoSitePlus; Q14258; -. DR SwissPalm; Q14258; -. DR BioMuta; TRIM25; -. DR DMDM; 313104033; -. DR EPD; Q14258; -. DR jPOST; Q14258; -. DR MassIVE; Q14258; -. DR MaxQB; Q14258; -. DR PaxDb; 9606-ENSP00000323889; -. DR PeptideAtlas; Q14258; -. DR ProteomicsDB; 59953; -. DR Pumba; Q14258; -. DR Antibodypedia; 1778; 594 antibodies from 38 providers. DR DNASU; 7706; -. DR Ensembl; ENST00000316881.9; ENSP00000323889.4; ENSG00000121060.19. DR Ensembl; ENST00000537230.3; ENSP00000445961.1; ENSG00000121060.19. DR GeneID; 7706; -. DR KEGG; hsa:7706; -. DR MANE-Select; ENST00000316881.9; ENSP00000323889.4; NM_005082.5; NP_005073.2. DR UCSC; uc002iut.4; human. DR AGR; HGNC:12932; -. DR CTD; 7706; -. DR DisGeNET; 7706; -. DR GeneCards; TRIM25; -. DR HGNC; HGNC:12932; TRIM25. DR HPA; ENSG00000121060; Low tissue specificity. DR MIM; 600453; gene. DR neXtProt; NX_Q14258; -. DR OpenTargets; ENSG00000121060; -. DR PharmGKB; PA37519; -. DR VEuPathDB; HostDB:ENSG00000121060; -. DR eggNOG; KOG2177; Eukaryota. DR GeneTree; ENSGT00940000160741; -. DR HOGENOM; CLU_013137_0_2_1; -. DR InParanoid; Q14258; -. DR OMA; KRGVHYW; -. DR OrthoDB; 5359093at2759; -. DR PhylomeDB; Q14258; -. DR TreeFam; TF351086; -. DR BRENDA; 2.3.2.27; 2681. DR PathwayCommons; Q14258; -. DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism. DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta. DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis. DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway. DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation. DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation. DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10. DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling. DR Reactome; R-HSA-9692916; SARS-CoV-1 activates/modulates innate immune responses. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR SignaLink; Q14258; -. DR SIGNOR; Q14258; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 7706; 17 hits in 1213 CRISPR screens. DR ChiTaRS; TRIM25; human. DR GeneWiki; TRIM25; -. DR GenomeRNAi; 7706; -. DR Pharos; Q14258; Tbio. DR PRO; PR:Q14258; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q14258; Protein. DR Bgee; ENSG00000121060; Expressed in ileal mucosa and 183 other cell types or tissues. DR ExpressionAtlas; Q14258; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProt. DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0039552; F:RIG-I binding; IPI:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:ARUK-UCL. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProt. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; EXP:Reactome. DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProt. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IDA:UniProt. DR GO; GO:0036503; P:ERAD pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB. DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProt. DR GO; GO:0006513; P:protein monoubiquitination; IMP:ParkinsonsUK-UCL. DR GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB. DR GO; GO:0046596; P:regulation of viral entry into host cell; IDA:UniProtKB. DR GO; GO:0043627; P:response to estrogen; IDA:UniProtKB. DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProt. DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl. DR GO; GO:0044790; P:suppression of viral release by host; IEA:Ensembl. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0019076; P:viral release from host cell; IMP:UniProtKB. DR CDD; cd19842; Bbox1_TRIM25-like_C-IV; 1. DR CDD; cd19776; Bbox2_TRIM25_C-IV; 1. DR CDD; cd16597; RING-HC_TRIM25_C-IV; 1. DR CDD; cd13736; SPRY_PRY_TRIM25; 1. DR Gene3D; 2.60.120.920; -; 1. DR Gene3D; 4.10.830.40; -; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR001870; B30.2/SPRY. DR InterPro; IPR043136; B30.2/SPRY_sf. DR InterPro; IPR003879; Butyrophylin_SPRY. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR006574; PRY. DR InterPro; IPR003877; SPRY_dom. DR InterPro; IPR042753; TRIM25_SPRY_PRY. DR InterPro; IPR027370; Znf-RING_euk. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR25465; B-BOX DOMAIN CONTAINING; 1. DR PANTHER; PTHR25465:SF40; E3 UBIQUITIN_ISG15 LIGASE TRIM25; 1. DR Pfam; PF13765; PRY; 1. DR Pfam; PF00622; SPRY; 1. DR Pfam; PF13445; zf-RING_UBOX; 1. DR PRINTS; PR01407; BUTYPHLNCDUF. DR SMART; SM00589; PRY; 1. DR SMART; SM00184; RING; 1. DR SMART; SM00449; SPRY; 1. DR SUPFAM; SSF57845; B-box zinc-binding domain; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS50188; B302_SPRY; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; Q14258; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Antiviral defense; Coiled coil; Cytoplasm; KW Host-virus interaction; Immunity; Innate immunity; Isopeptide bond; Ligase; KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transferase; KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..630 FT /note="E3 ubiquitin/ISG15 ligase TRIM25" FT /id="PRO_0000056233" FT DOMAIN 439..630 FT /note="B30.2/SPRY" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT ZN_FING 13..54 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 180..450 FT /note="Interaction with influenza A virus NS1" FT REGION 355..403 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 217..307 FT /evidence="ECO:0000255" FT COMPBIAS 368..393 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 13 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007744|PDB:5EYA, ECO:0007744|PDB:5FER" FT BINDING 16 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007744|PDB:5EYA, ECO:0007744|PDB:5FER" FT BINDING 28 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:5EYA, ECO:0007744|PDB:5FER" FT BINDING 30 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:5EYA, ECO:0007744|PDB:5FER" FT BINDING 33 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007744|PDB:5EYA, ECO:0007744|PDB:5FER" FT BINDING 36 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007744|PDB:5EYA, ECO:0007744|PDB:5FER" FT BINDING 50 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:5EYA, ECO:0007744|PDB:5FER" FT BINDING 53 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:5EYA, ECO:0007744|PDB:5FER" FT MOD_RES 91 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 273 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 278 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 567 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT CROSSLNK 117 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000269|PubMed:17222803" FT VARIANT 89 FT /note="V -> G (in dbSNP:rs7212260)" FT /id="VAR_024614" FT VARIANT 358 FT /note="P -> L (in dbSNP:rs205498)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:8248217, ECO:0007744|PubMed:21269460" FT /id="VAR_024615" FT MUTAGEN 21 FT /note="K->R: No effect on ISGylation." FT /evidence="ECO:0000269|PubMed:17222803" FT MUTAGEN 50 FT /note="C->S: Almost complete loss of ZAP/ZC3HAV1 FT ubiquitination; when associated with S-53." FT /evidence="ECO:0000269|PubMed:28202764" FT MUTAGEN 53 FT /note="C->S: Almost complete loss of ZAP/ZC3HAV1 FT ubiquitination; when associated with S-50." FT /evidence="ECO:0000269|PubMed:28202764" FT MUTAGEN 54 FT /note="R->P: Complete loss of viral inhibition FT independently of the host interferon response." FT /evidence="ECO:0000269|PubMed:36067236" FT MUTAGEN 65 FT /note="K->A: Almost complete loss of ubiquitination FT activity." FT /evidence="ECO:0000269|PubMed:27425606" FT MUTAGEN 65 FT /note="K->R: No effect on ISGylation." FT /evidence="ECO:0000269|PubMed:17222803" FT MUTAGEN 71 FT /note="N->D: Almost complete loss of ubiquitination FT activity." FT /evidence="ECO:0000269|PubMed:27425606" FT MUTAGEN 112 FT /note="K->R: No effect on ISGylation." FT /evidence="ECO:0000269|PubMed:17222803" FT MUTAGEN 117 FT /note="K->R: No ISGylation." FT /evidence="ECO:0000269|PubMed:17222803" FT HELIX 2..5 FT /evidence="ECO:0007829|PDB:5EYA" FT HELIX 7..10 FT /evidence="ECO:0007829|PDB:5FER" FT TURN 14..16 FT /evidence="ECO:0007829|PDB:5FER" FT STRAND 17..19 FT /evidence="ECO:0007829|PDB:5FER" FT STRAND 21..25 FT /evidence="ECO:0007829|PDB:5FER" FT STRAND 31..33 FT /evidence="ECO:0007829|PDB:5FER" FT HELIX 34..43 FT /evidence="ECO:0007829|PDB:5FER" FT STRAND 46..49 FT /evidence="ECO:0007829|PDB:5FER" FT TURN 51..53 FT /evidence="ECO:0007829|PDB:5FER" FT STRAND 56..59 FT /evidence="ECO:0007829|PDB:5FER" FT HELIX 67..78 FT /evidence="ECO:0007829|PDB:5FER" FT HELIX 191..300 FT /evidence="ECO:0007829|PDB:4LTB" FT HELIX 307..316 FT /evidence="ECO:0007829|PDB:4LTB" FT HELIX 331..358 FT /evidence="ECO:0007829|PDB:4LTB" FT HELIX 435..445 FT /evidence="ECO:0007829|PDB:6FLM" FT HELIX 449..453 FT /evidence="ECO:0007829|PDB:6FLM" FT TURN 463..465 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 470..473 FT /evidence="ECO:0007829|PDB:6FLM" FT TURN 474..477 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 478..481 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 496..504 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 507..520 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 522..530 FT /evidence="ECO:0007829|PDB:6FLM" FT HELIX 538..540 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 548..554 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 557..562 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 565..568 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 576..582 FT /evidence="ECO:0007829|PDB:6FLM" FT TURN 583..586 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 587..604 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 611..617 FT /evidence="ECO:0007829|PDB:6FLM" FT STRAND 623..626 FT /evidence="ECO:0007829|PDB:6FLM" SQ SEQUENCE 630 AA; 70973 MW; EB0AB353F0AD4C80 CRC64; MAELCPLAEE LSCSICLEPF KEPVTTPCGH NFCGSCLNET WAVQGSPYLC PQCRAVYQAR PQLHKNTVLC NVVEQFLQAD LAREPPADVW TPPARASAPS PNAQVACDHC LKEAAVKTCL VCMASFCQEH LQPHFDSPAF QDHPLQPPVR DLLRRKCSQH NRLREFFCPE HSECICHICL VEHKTCSPAS LSQASADLEA TLRHKLTVMY SQINGASRAL DDVRNRQQDV RMTANRKVEQ LQQEYTEMKA LLDASETTST RKIKEEEKRV NSKFDTIYQI LLKKKSEIQT LKEEIEQSLT KRDEFEFLEK ASKLRGISTK PVYIPEVELN HKLIKGIHQS TIDLKNELKQ CIGRLQEPTP SSGDPGEHDP ASTHKSTRPV KKVSKEEKKS KKPPPVPALP SKLPTFGAPE QLVDLKQAGL EAAAKATSSH PNSTSLKAKV LETFLAKSRP ELLEYYIKVI LDYNTAHNKV ALSECYTVAS VAEMPQNYRP HPQRFTYCSQ VLGLHCYKKG IHYWEVELQK NNFCGVGICY GSMNRQGPES RLGRNSASWC VEWFNTKISA WHNNVEKTLP STKATRVGVL LNCDHGFVIF FAVADKVHLM YKFRVDFTEA LYPAFWVFSA GATLSICSPK //