TRIM63

TRIM63
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3DDT, 4M3L, 2D8U
Identifiers
Aliases	TRIM63, IRF, MURF1, MURF2, RNF28, SMRZ, tripartite motif containing 63
External IDs	OMIM: 606131 MGI: 2447992 HomoloGene: 41878 GeneCards: TRIM63
Gene location (Human)
Chr.	Chromosome 1 (human)[1]
End	26,068,436 bp[1]
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)[2]
End	134,329,629 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• zinc ion binding; • GO:0001948 protein binding; • titin binding; • signal transducer activity; • metal ion binding; • ubiquitin-protein transferase activity; • transferase activity;
Cellular component	• cytoplasm; • M band; • contractile fiber; • Z disc; • microtubules; • cell nucleus; • intracellular;
Biological process	• skeletal muscle atrophy; • muscle contraction; • response to glucocorticoid; • response to interleukin-1; • protein ubiquitination; • response to electrical stimulus involved in regulation of muscle adaptation; • signal transduction; • negative regulation of cardiac muscle hypertrophy;
	Sources:Amigo / QuickGO
Orthologs
	84676
	433766
	ENSG00000158022
	ENSMUSG00000028834
	Q969Q1
	Q38HM4
	NM_032588
	NM_001039048; NM_001369245
	NP_115977
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

E3 ubiquitin-protein ligase TRIM63, also known as "MuRF1" is an enzyme that in humans is encoded by the TRIM63 gene.[5][6][7]

This gene encodes a member of the RING zinc finger protein family found in striated muscle and iris. The product of this gene is localized to the Z-line and M-line lattices of myofibrils, where titin's N-terminal and C-terminal regions respectively bind to the sarcomere. In vitro binding studies have shown that this protein also binds directly to titin near the region of titin containing kinase activity. Another member of this protein family binds to microtubules. Since these family members can form heterodimers, this suggests that these proteins may serve as a link between titin kinase and microtubule-dependent signal pathways in muscle.[7]

The protein encoded by the Trim63 gene is also called MuRF1. MuRF1 is the name most commonly used in the literature, and it stands for "Muscle RING Finger 1." Structurally, there are two closely related MuRFs, MuRF2 and MuRF3. These also have TRIM codes: MuRF2 is TRIM55; MuRF3 is TRIM54.

Interactions

Trim63/MuRF1 has been shown to be an E3 ubiquitin ligase. Its major substrate is Myosin Heavy Chain. MuRF1 is upregulated during skeletal muscle atrophy – and thus the degradation of myosin heavy chain, which is a major component of the sarcomere, is an important mechanism in the breakdown of skeletal muscle under atrophy conditions. MuRF1 has been shown to be upregulated during denervation, administration of glucocorticoids, immobilization, and casting (when a cast is applied to a limb, in order to immoblize it). All of these treatments cause skeletal muscle atrophy.

TRIM63 has been shown to interact with Titin,[5] GMEB1[8] and SUMO2.[6]

Clinical Significance

Recently, it has been suggested that TRIM63 is associated with an autosomal-recessive form of hypertrophic cardiomyopathy (HCM).[9] In this paper, the authors describe that individuals harboring homozygous or compound heterozygous rare variants in TRIM63 show a peculiar HCM phenotype, characterized by concentric left ventricular (LV) hypertrophy (50% of patients) and a high rate of LV dysfunction (20%).

References

GRCh38: Ensembl release 89: ENSG00000158022 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000028834 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Centner T, Yano J, Kimura E, McElhinny AS, Pelin K, Witt CC, Bang ML, Trombitas K, Granzier H, Gregorio CC, Sorimachi H, Labeit S (Mar 2001). "Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain". J Mol Biol. 306 (4): 717–26. doi:10.1006/jmbi.2001.4448. PMID 11243782.
Dai KS, Liew CC (Jun 2001). "A novel human striated muscle RING zinc finger protein, SMRZ, interacts with SMT3b via its RING domain". J Biol Chem. 276 (26): 23992–9. doi:10.1074/jbc.M011208200. PMID 11283016.
"Entrez Gene: TRIM63 tripartite motif-containing 63".
McElhinny AS, Kakinuma K, Sorimachi H, Labeit S, Gregorio CC (April 2002). "Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1". J. Cell Biol. 157 (1): 125–36. doi:10.1083/jcb.200108089. PMC 2173255. PMID 11927605.
Salazar-Mendiguchía, Joel; Ochoa, Juan Pablo; Palomino-Doza, Julian; Domínguez, Fernando; Díez-López, Carles; Akhtar, Mohammed; Ramiro-León, Soraya; Clemente, María M; Pérez-Cejas, Antonia; Robledo, María; Gómez-Díaz, Iria (September 2020). "Mutations in TRIM63 cause an autosomal-recessive form of hypertrophic cardiomyopathy". Heart. 106 (17): 1342–1348. doi:10.1136/heartjnl-2020-316913. ISSN 1355-6037. PMC 7476281. PMID 32451364.

Bodine SC, Latres E, Baumhueter S, et al. (2001). "Identification of ubiquitin ligases required for skeletal muscle atrophy". Science. 294 (5547): 1704–8. Bibcode:2001Sci...294.1704B. doi:10.1126/science.1065874. PMID 11679633. S2CID 37349291.
McElhinny AS, Kakinuma K, Sorimachi H, et al. (2002). "Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1". J. Cell Biol. 157 (1): 125–36. doi:10.1083/jcb.200108089. PMC 2173255. PMID 11927605.
Wistow G, Bernstein SL, Ray S, et al. (2002). "Expressed sequence tag analysis of adult human iris for the NEIBank Project: steroid-response factors and similarities with retinal pigment epithelium". Mol. Vis. 8: 185–95. PMID 12107412.
Pizon V, Iakovenko A, Van Der Ven PF, et al. (2003). "Transient association of titin and myosin with microtubules in nascent myofibrils directed by the MURF2 RING-finger protein". J. Cell Sci. 115 (Pt 23): 4469–82. doi:10.1242/jcs.00131. PMID 12414993.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Kedar V, McDonough H, Arya R, et al. (2005). "Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I." Proc. Natl. Acad. Sci. U.S.A. 101 (52): 18135–40. doi:10.1073/pnas.0404341102. PMC 539735. PMID 15601779.
Witt SH, Granzier H, Witt CC, Labeit S (2005). "MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly: towards understanding MURF-dependent muscle ubiquitination". J. Mol. Biol. 350 (4): 713–22. doi:10.1016/j.jmb.2005.05.021. PMID 15967462.
Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID 16710414.
Doucet M, Russell AP, Léger B, et al. (2007). "Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease". Am. J. Respir. Crit. Care Med. 176 (3): 261–9. doi:10.1164/rccm.200605-704OC. PMID 17478621.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000158022 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028834 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid11243782-5] Centner T, Yano J, Kimura E, McElhinny AS, Pelin K, Witt CC, Bang ML, Trombitas K, Granzier H, Gregorio CC, Sorimachi H, Labeit S (Mar 2001). "Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain". J Mol Biol. 306 (4): 717–26. doi:10.1006/jmbi.2001.4448. PMID 11243782.

[pmid11283016-6] Dai KS, Liew CC (Jun 2001). "A novel human striated muscle RING zinc finger protein, SMRZ, interacts with SMT3b via its RING domain". J Biol Chem. 276 (26): 23992–9. doi:10.1074/jbc.M011208200. PMID 11283016.

[entrez-7] "Entrez Gene: TRIM63 tripartite motif-containing 63".

[pmid11927605-8] McElhinny AS, Kakinuma K, Sorimachi H, Labeit S, Gregorio CC (April 2002). "Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1". J. Cell Biol. 157 (1): 125–36. doi:10.1083/jcb.200108089. PMC 2173255. PMID 11927605.

[9] Salazar-Mendiguchía, Joel; Ochoa, Juan Pablo; Palomino-Doza, Julian; Domínguez, Fernando; Díez-López, Carles; Akhtar, Mohammed; Ramiro-León, Soraya; Clemente, María M; Pérez-Cejas, Antonia; Robledo, María; Gómez-Díaz, Iria (September 2020). "Mutations in TRIM63 cause an autosomal-recessive form of hypertrophic cardiomyopathy". Heart. 106 (17): 1342–1348. doi:10.1136/heartjnl-2020-316913. ISSN 1355-6037. PMC 7476281. PMID 32451364.

TRIM63

Interactions

Clinical Significance

References

Further reading