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FLASH GENE

Symbol

TRIM63

contributors: mct - updated : 25-10-2013

HGNC name	tripartite motif-containing 63
HGNC id	16007

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CMH15 cardiomyopathy, familial, hypertrophic, 15
Location	1p36.11      Physical location : 26.377.797 - 26.394.121
Synonym name	iris ring finger protein
	muscle specific ring finger protein 1
	striated muscle RING zinc finger protein
	ring finger protein 28
Synonym symbol(s)	IRF, SMRZ, MURF1, MURF2, MURF-1, MURF-2, RNF28, FLJ32380
EC.number	6.3.2.-

DNA

TYPE	functioning gene
STRUCTURE	16.32 kb     9 Exon(s)

regulatory sequence	Binding site   transcription factor
text structure	promoter containing a near-perfect palindromic glucocorticoid response element (GRE) 200 base pairs upstream of the transcription start site (Waddell 2008)

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D1S234 - D1S2885 - TRIM63 - D1S455 - D1S2749 - cen
Authors	UCSC (2009)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_032588 9 - 1771 NP_115977 40.1 353 - -

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Homo sapiens Nervous brain         Respiratory lung         Visual eye anterior segment iris

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone       Muscular striatum cardiac   specific Homo sapiens Muscular striatum skeletal   specific Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	heart highly, all striated muscle tissues throughout development

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a ring finger motif in the N-terminus
	a zing-binding type-2 B-box motif
	a coiled-coil dimerization motif box in the central region (RBCQ) tripartite motif (TRIM)
	a COS (C-terminal subgroup one signature) domain

conjugated

MetalloP

mono polymer

homomer , heteromer , oligo

HOMOLOGY

interspecies	homolog to rattus Trim63 (91.1 pc)
	homolog to murine Trim63 (92.6 pc)

Homologene

FAMILY	C-II TRIM family
	C3HC4 RING finger subfamily
	MURF subfamily
	RBCC family

CATEGORY

enzyme , regulatory , DNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus,chromatin/chromosome
text	Z line and M line lattices of myofibrils

basic FUNCTION	sarcomere-associated protein, involved in the cell cycle regulatory process of striated muscle cells
	playing a role in striated muscle cell embryonic development
	may coordinately regulate the energy metabolism of mitochondrial and cytoplasmic compartments
	acting as an E3 ubiquitin ligase (Ozato 2008)
	regulating proteasomal degradation of cardiac troponin I/TNNI3 and probably of other sarcomeric-associated proteins
	may regulate the organization of myofibrils through TTN in muscle cells
	involved in regulating muscle trophic homeostasis through interactions with a number of proteins including glycogen phosphorylase and FOXO (Forkhead box, subgroup O)
	plays an important role in regulating cardiac size through alterations in protein turnover and that MuRF1 is not required to induce cardiac atrophy
	muscle RING finger protein which is involved in muscle wasting
	is involved in disuse-induced bone loss in both of the two major bone remodeling activities, osteoblastic bone formation and osteoclastic bone resorption
	is responsible for mediating muscle atrophy that occurs during the period of active lung injury in humans, and skeletal muscle dysfunction persists despite resolution of lung injury
	FBXO32 and TRIM63 are two E3 ubiquitin ligases that are important regulators of ubiquitin-mediated protein degradation in skeletal muscle
	maintains muscle protein homeostasis by tagging the sarcomere proteins with ubiquitin for subsequent degradation by the ubiquitin-proteasome system (UPS)

CELLULAR PROCESS	cell cycle
	protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	interacting with SUMO2, titin/TTN and GMEB1
	interacting with TRIM54 and probably with TRIM55 and TNNI3
	forming a ternary complex with GNB2L1 and PRKCE
	binding to titin repeats, near the titin kinase domain, important for the stability of M-line region and thick filament structure
	binding to ubiquitin (UBC9) conjugating enzyme 9 and isopeptidase
	binding with glucocorticoid modulatory element binding protein-1 (GMEB1) suggesting that RNF28 may link myofibril signaling pathways and influences muscle gene expression
	interacting with TNNI1, and TNNI2 (targeted for ubiquitylation and proteasome-depoendent degradation)
	indirectly reduces MYBPC3 levels by regulating the transcription of myosin heavy chains (
	FOXO3 and SMAD3, converge to coordinately and directly regulate transcription of TRIM63

cell & other

REGULATION

induced by	FOXO1
		FOXO3

Other

developmentally regulated

ASSOCIATED DISORDERS

corresponding disease(s)

CMH15

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular     inhibition of TRIM63 could be a novel mechanism to prevent or reverse muscle wasting associated with various pathologies

ANIMAL & CELL MODELS

	murf1 knock out mice (Bodine 2001)
	the increase in cardiac size in MuRF1 KO mice was related to a decrease in proteasome activity and an increase in Akt signaling relative to WT mice