TRI63_MOUSE
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 03-AUG-2022, entry version 115.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION AS AN E3 UBIQUITIN LIGASE,
RP 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., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., 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., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., 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 expression
RT of genes for specific E2 and E3 proteins in skeletal muscle 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 prevents
RT 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. Regulates
CC the proteasomal degradation of muscle proteins under amino acid
CC starvation, where muscle protein is catabolized to provide other organs
CC with amino acids. Inhibits de novo skeletal muscle protein synthesis
CC under amino acid starvation. Regulates proteasomal degradation of
CC cardiac troponin I/TNNI3 and probably of other sarcomeric-associated
CC proteins. May play a role in striated muscle atrophy and hypertrophy by
CC regulating an anti-hypertrophic PKC-mediated signaling pathway. May
CC regulate the 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:
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. Homooligomer and heterooligomer. Interacts with
CC SUMO2, titin/TTN and GMEB1. Interacts with TRIM54 and probably with
CC TRIM55 (By similarity). Interacts with TNNI3. Forms a ternary complex
CC with RACK1 and PRKCE. Interacts with CKM. {ECO:0000250,
CC ECO:0000269|PubMed:15596539, ECO:0000269|PubMed:15601779,
CC ECO:0000269|PubMed:18222470}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15601779}. Nucleus
CC {ECO:0000269|PubMed:15601779}. Cytoplasm, myofibril, sarcomere, M line
CC {ECO:0000250}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000250}.
CC Note=Localizes to the M- and Z-lines in skeletal muscle (By
CC similarity). Colocalizes with TNNI3 in 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 -!- INDUCTION: By hydrogen peroxide. Up-regulated in response to amino acid
CC starvation. {ECO:0000269|PubMed:12773310, ECO:0000269|PubMed:18222470}.
CC -!- DOMAIN: The RING-type zinc finger mediates interaction with SUMO2 and
CC localization to the nucleus (By similarity). Also required for the E3
CC ubiquitin ligase activity. {ECO:0000250, 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 conditions.
CC Under amino acid starvation, mice continue to synthesize muscle protein
CC and degrade less muscle protein than wild-type, leading to a decrease
CC in the blood levels of free amino acids. Besides, mutant mice display
CC higher creatine kinase activity under amino acid starvation.
CC {ECO:0000269|PubMed:18222470}.
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DR EMBL; DQ229108; ABB16283.1; -; mRNA.
DR EMBL; AK052911; BAC35199.1; -; mRNA.
DR AlphaFoldDB; Q38HM4; -.
DR SMR; Q38HM4; -.
DR IntAct; Q38HM4; 2.
DR STRING; 10090.ENSMUSP00000101501; -.
DR iPTMnet; Q38HM4; -.
DR PhosphoSitePlus; Q38HM4; -.
DR PaxDb; Q38HM4; -.
DR PRIDE; Q38HM4; -.
DR ProteomicsDB; 259324; -. [Q38HM4-1]
DR ProteomicsDB; 259325; -. [Q38HM4-2]
DR UCSC; uc008ves.1; mouse. [Q38HM4-2]
DR MGI; MGI:2447992; Trim63.
DR eggNOG; KOG2177; Eukaryota.
DR InParanoid; Q38HM4; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q38HM4; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q38HM4; protein.
DR GO; GO:0043292; C:contractile fiber; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0004842; F:ubiquitin-protein transferase activity; ISO: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; ISO:MGI.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:CACAO.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
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; cd16759; RING-HC_MuRF1; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR017903; COS_domain.
DR InterPro; IPR042667; TRIM63_RING-HC.
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; Cytoplasm; Direct protein sequencing;
KW Metal-binding; Muscle protein; Nucleus; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..350
FT /note="E3 ubiquitin-protein ligase TRIM63"
FT /id="PRO_0000056291"
FT DOMAIN 267..325
FT /note="COS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00586"
FT ZN_FING 23..79
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 117..159
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT REGION 74..218
FT /note="Interaction with TTN"
FT /evidence="ECO:0000250"
FT REGION 325..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 207..269
FT /evidence="ECO:0000255"
FT COMPBIAS 325..343
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 125
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT VAR_SEQ 111..151
FT /note="SRPLQKGSHPMCKEHEDEKINIYCLTCEVPTCSLCKVFGAH -> RSVCSRT
FT APPLPQAPPTSRSLQLLSPAQRASTLYRRQNLSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016647"
FT VAR_SEQ 152..350
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016648"
FT CONFLICT 6
FT /note="G -> S (in Ref. 2; BAC35199)"
FT /evidence="ECO:0000305"
FT CONFLICT 42
FT /note="N -> D (in Ref. 2; BAC35199)"
FT /evidence="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
