ID TRI63_MOUSE Reviewed; 350 AA. AC Q38HM4; Q8BWC4; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 22-NOV-2005, sequence version 1. DT 10-MAY-2017, entry version 98. DE RecName: Full=E3 ubiquitin-protein ligase TRIM63; DE EC=2.3.2.27; DE AltName: Full=Muscle-specific RING finger protein 1; DE Short=MuRF-1; DE Short=MuRF1; DE Short=Muscle RING finger protein 1; DE AltName: Full=RING-type E3 ubiquitin transferase TRIM63 {ECO:0000305}; DE AltName: Full=Tripartite motif-containing protein 63; GN Name=Trim63; Synonyms=Murf1, Rf1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION AS AN E3 UBIQUITIN RP LIGASE, INTERACTION WITH TNNI3, DOMAIN, AND SUBCELLULAR LOCATION. RC STRAIN=C57BL/6J; RX PubMed=15601779; DOI=10.1073/pnas.0404341102; RA Kedar V., McDonough H., Arya R., Li H.-H., Rockman H.A., Patterson C.; RT "Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that RT degrades cardiac troponin I."; RL Proc. Natl. Acad. Sci. U.S.A. 101:18135-18140(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Heart; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP PROTEIN SEQUENCE OF 197-212, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=OF1; TISSUE=Hippocampus; RA Lubec G., Sunyer B., Chen W.-Q.; RL Submitted (JAN-2009) to UniProtKB. RN [4] RP INDUCTION. RX PubMed=12773310; DOI=10.1152/ajpcell.00129.2003; RA Li Y.-P., Chen Y., Li A.S., Reid M.B.; RT "Hydrogen peroxide stimulates ubiquitin-conjugating activity and RT expression of genes for specific E2 and E3 proteins in skeletal muscle RT myotubes."; RL Am. J. Physiol. 285:C806-C812(2003). RN [5] RP FUNCTION, AND INTERACTION WITH RACK1 AND PRKCE. RX PubMed=15596539; DOI=10.1083/jcb.200402033; RA Arya R., Kedar V., Hwang J.R., McDonough H., Li H.-H., Taylor J., RA Patterson C.; RT "Muscle ring finger protein-1 inhibits PKC-epsilon activation and RT prevents cardiomyocyte hypertrophy."; RL J. Cell Biol. 167:1147-1159(2004). RN [6] RP DISRUPTION PHENOTYPE, FUNCTION, INTERACTION WITH CKM, AND INDUCTION. RX PubMed=18222470; DOI=10.1016/j.jmb.2007.11.049; RA Koyama S., Hata S., Witt C.C., Ono Y., Lerche S., Ojima K., Chiba T., RA Doi N., Kitamura F., Tanaka K., Abe K., Witt S.H., Rybin V., Gasch A., RA Franz T., Labeit S., Sorimachi H.; RT "Muscle RING-finger protein-1 (MuRF1) as a connector of muscle energy RT metabolism and protein synthesis."; RL J. Mol. Biol. 376:1224-1236(2008). CC -!- FUNCTION: E3 ubiquitin ligase. Mediates the ubiquitination and CC subsequent proteasomal degradation of CKM, GMEB1 and HIBADH. CC Regulates the proteasomal degradation of muscle proteins under CC amino acid starvation, where muscle protein is catabolized to CC provide other organs with amino acids. Inhibits de novo skeletal CC muscle protein synthesis under amino acid starvation. Regulates CC proteasomal degradation of cardiac troponin I/TNNI3 and probably CC of other sarcomeric-associated proteins. May play a role in CC striated muscle atrophy and hypertrophy by regulating an anti- CC hypertrophic PKC-mediated signaling pathway. May regulate the CC organization of myofibrils through TTN in muscle cells. CC {ECO:0000269|PubMed:15596539, ECO:0000269|PubMed:15601779, CC ECO:0000269|PubMed:18222470}. CC -!- CATALYTIC ACTIVITY: S-ubiquitinyl-[E2 ubiquitin-conjugating CC enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin- CC conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor CC protein]-L-lysine. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Homodimer. Homooligomer and heterooligomer. Interacts CC with SUMO2, titin/TTN and GMEB1. Interacts with TRIM54 and CC probably with TRIM55 (By similarity). Interacts with TNNI3. Forms CC a ternary complex with RACK1 and PRKCE. Interacts with CKM. CC {ECO:0000250, ECO:0000269|PubMed:15596539, CC ECO:0000269|PubMed:15601779, ECO:0000269|PubMed:18222470}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15601779}. CC Nucleus {ECO:0000269|PubMed:15601779}. Cytoplasm, myofibril, CC sarcomere, M line {ECO:0000250}. Cytoplasm, myofibril, sarcomere, CC Z line {ECO:0000250}. Note=Localizes to the M- and Z-lines in CC skeletal muscle (By similarity). Colocalizes with TNNI3 in CC myocytes. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q38HM4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q38HM4-2; Sequence=VSP_016647, VSP_016648; CC Note=No experimental confirmation available.; CC -!- INDUCTION: By hydrogen peroxide. Up-regulated in response to amino CC acid starvation. {ECO:0000269|PubMed:12773310, CC ECO:0000269|PubMed:18222470}. CC -!- DOMAIN: The RING-type zinc finger mediates interaction with SUMO2 CC and localization to the nucleus (By similarity). Also required for CC the E3 ubiquitin ligase activity. {ECO:0000250, CC ECO:0000269|PubMed:15601779}. CC -!- DOMAIN: The B box-type zinc finger mediates homodimerization. CC {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: No visible phenotype under normal CC conditions. Under amino acid starvation, mice continue to CC synthesize muscle protein and degrade less muscle protein than CC wild-type, leading to a decrease in the blood levels of free amino CC acids. Besides, mutant mice display higher creatine kinase CC activity under amino acid starvation. CC {ECO:0000269|PubMed:18222470}. 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; DQ229108; ABB16283.1; -; mRNA. DR EMBL; AK052911; BAC35199.1; -; mRNA. DR UniGene; Mm.331961; -. DR ProteinModelPortal; Q38HM4; -. DR SMR; Q38HM4; -. DR STRING; 10090.ENSMUSP00000101501; -. DR iPTMnet; Q38HM4; -. DR PhosphoSitePlus; Q38HM4; -. DR PaxDb; Q38HM4; -. DR PRIDE; Q38HM4; -. DR UCSC; uc008ves.1; mouse. [Q38HM4-2] DR MGI; MGI:2447992; Trim63. DR eggNOG; ENOG410ITEN; Eukaryota. DR eggNOG; ENOG4110918; LUCA. DR HOVERGEN; HBG071242; -. DR InParanoid; Q38HM4; -. DR UniPathway; UPA00143; -. DR PRO; PR:Q38HM4; -. DR Proteomes; UP000000589; Unplaced. DR CleanEx; MM_TRIM63; -. DR GO; GO:0043292; C:contractile fiber; ISA:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0031430; C:M band; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell. DR GO; GO:0031432; F:titin binding; ISO:MGI. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:MGI. DR GO; GO:0006936; P:muscle contraction; ISA:MGI. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI. DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI. DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; IDA:UniProtKB. DR GO; GO:0014878; P:response to electrical stimulus involved in regulation of muscle adaptation; ISS:UniProtKB. DR CDD; cd00162; RING; 1. DR Gene3D; 3.30.40.10; -; 1. DR InterPro; IPR017903; COS_domain. DR InterPro; IPR027370; Znf-RING_LisH. DR InterPro; IPR000315; Znf_B-box. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR Pfam; PF00643; zf-B_box; 1. DR Pfam; PF13445; zf-RING_UBOX; 1. DR SMART; SM00336; BBOX; 1. DR SMART; SM00184; RING; 1. DR PROSITE; PS51262; COS; 1. DR PROSITE; PS50119; ZF_BBOX; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Coiled coil; Complete proteome; Cytoplasm; KW Direct protein sequencing; Metal-binding; Muscle protein; Nucleus; KW Reference proteome; Transferase; Ubl conjugation pathway; Zinc; KW Zinc-finger. FT CHAIN 1 350 E3 ubiquitin-protein ligase TRIM63. FT /FTId=PRO_0000056291. FT DOMAIN 267 325 COS. {ECO:0000255|PROSITE- FT ProRule:PRU00586}. FT ZN_FING 23 79 RING-type. {ECO:0000255|PROSITE- FT ProRule:PRU00175}. FT ZN_FING 117 159 B box-type. {ECO:0000255|PROSITE- FT ProRule:PRU00024}. FT REGION 74 218 Interaction with TTN. {ECO:0000250}. FT COILED 207 269 {ECO:0000255}. FT VAR_SEQ 111 151 SRPLQKGSHPMCKEHEDEKINIYCLTCEVPTCSLCKVFGAH FT -> RSVCSRTAPPLPQAPPTSRSLQLLSPAQRASTLYRRQN FT LSS (in isoform 2). FT {ECO:0000303|PubMed:16141072}. FT /FTId=VSP_016647. FT VAR_SEQ 152 350 Missing (in isoform 2). FT {ECO:0000303|PubMed:16141072}. FT /FTId=VSP_016648. FT CONFLICT 6 6 G -> S (in Ref. 2; BAC35199). FT {ECO:0000305}. FT CONFLICT 42 42 N -> D (in Ref. 2; BAC35199). FT {ECO:0000305}. SQ SEQUENCE 350 AA; 39491 MW; 1840B7BB2F77DEC1 CRC64; MDYKSGLIPD GNAMENLEKQ LICPICLEMF TKPVVILPCQ HNLCRKCAND IFQAANPYWT NRGGSVSMSG GRFRCPSCRH EVIMDRHGVY GLQRNLLVEN IIDIYKQECS SRPLQKGSHP MCKEHEDEKI NIYCLTCEVP TCSLCKVFGA HQACEVAPLQ SIFQGQKTEL SNCISMLVAG NDRVQTIISQ LVDSCRVTKE NSHQVKEELS QKFDTLYAIL DEKKSELLQR ITQEQEEKLG FIEALILQYR EQLEKSTKLV ETAIQSLDEP GGATFLSSAK QLIKSNVEAS KGCQLGKTEQ GFENMDYFTL DLEHIAEALR AIDFGTDEEE EEFTEEEADE EEGVTTEGHQ //