TRIM54

Summary

TRIM54 (tripartite motif containing 54, HGNC:16008) is a protein-coding gene on chromosome 2p23.3, encoding Tripartite motif-containing protein 54 (Q9BYV2). May bind and stabilize microtubules during myotubes formation.

The protein encoded by this gene contains a RING finger motif and is highly similar to the ring finger proteins RNF28/MURF1 and RNF29/MURF2. In vitro studies demonstrated that this protein, RNF28, and RNF29 form heterodimers, which may be important for the regulation of titin kinase and microtubule-dependent signal pathways in striated muscles. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 57159 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 83 total
• MANE Select transcript: NM_187841

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16008
Approved symbol	TRIM54
Name	tripartite motif containing 54
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	MURF, MURF-3
Ensembl gene	ENSG00000138100
Ensembl biotype	protein_coding
OMIM	606474
Entrez	57159

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 retained_intron

ENST00000296098, ENST00000380075, ENST00000485306, ENST00000488321, ENST00000884194, ENST00000884195, ENST00000884196, ENST00000884197, ENST00000884198, ENST00000884199, ENST00000884200, ENST00000929727, ENST00000950493, ENST00000950494, ENST00000950495

RefSeq mRNA: 2 — MANE Select: NM_187841 NM_032546, NM_187841

CCDS: CCDS1745, CCDS1746

Canonical transcript exons

ENST00000380075 — 9 exons

Exon	Start	End
ENSE00000962977	27305584	27305817
ENSE00000962979	27306213	27306337
ENSE00001078299	27298567	27298739
ENSE00001078301	27304959	27305054
ENSE00001078303	27299245	27299416
ENSE00001136072	27282429	27282899
ENSE00001180045	27306456	27306542
ENSE00001381278	27306887	27307435
ENSE00003503703	27306080	27306102

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 99.39.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2267 / max 863.2606, expressed in 192 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19347	4.0924	189
19346	0.0930	48
19348	0.0412	22

Top tissues by expression

249 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.39	gold quality
gastrocnemius	UBERON:0001388	99.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.95	gold quality
right atrium auricular region	UBERON:0006631	97.76	gold quality
heart left ventricle	UBERON:0002084	97.73	gold quality
cardiac ventricle	UBERON:0002082	97.22	gold quality
muscle of leg	UBERON:0001383	96.97	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.71	gold quality
cardiac atrium	UBERON:0002081	96.48	gold quality
skeletal muscle tissue	UBERON:0001134	94.78	gold quality
quadriceps femoris	UBERON:0001377	92.88	gold quality
tibialis anterior	UBERON:0001385	92.80	gold quality
heart	UBERON:0000948	92.72	gold quality
vastus lateralis	UBERON:0001379	92.71	gold quality
right testis	UBERON:0004534	92.62	gold quality
left testis	UBERON:0004533	92.50	gold quality
deltoid	UBERON:0001476	92.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.21	gold quality
biceps brachii	UBERON:0001507	90.61	gold quality
left ventricle myocardium	UBERON:0006566	90.59	silver quality
muscle tissue	UBERON:0002385	88.85	gold quality
heart right ventricle	UBERON:0002080	88.38	gold quality
testis	UBERON:0000473	87.92	gold quality
myocardium	UBERON:0002349	87.84	silver quality
left adrenal gland cortex	UBERON:0035825	83.15	gold quality
right adrenal gland cortex	UBERON:0035827	83.02	gold quality
right adrenal gland	UBERON:0001233	82.37	gold quality
left adrenal gland	UBERON:0001234	82.33	gold quality
right frontal lobe	UBERON:0002810	81.98	gold quality
adrenal cortex	UBERON:0001235	81.02	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting TRIM54, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-885-3P	95.14	63.08	448
HSA-MIR-4520-5P	93.54	65.23	140

Literature-anchored findings (GeneRIF, showing 3)

• Functional analysis of the mouse counterpart. (PMID:10953002)
• A novel protein aggregate myopathies and cardiomyopathy resulting from combined homozygous MuRF1 null mutation and heterozygous MuRF3 missense mutation. (PMID:25801283)
• Sorafenib induces ferroptosis by promoting TRIM54-mediated FSP1 ubiquitination and degradation in hepatocellular carcinoma. (PMID:37695069)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim54	ENSDARG00000029907
mus_musculus	Trim54	ENSMUSG00000062077
rattus_norvegicus	Trim54	ENSRNOG00000006146

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

Tripartite motif-containing protein 54 — Q9BYV2 (reviewed: Q9BYV2)

Alternative names: Muscle-specific RING finger protein, Muscle-specific RING finger protein 3, RING finger protein 30

All UniProt accessions (1): Q9BYV2

UniProt curated annotations — full annotation on UniProt →

Function. May bind and stabilize microtubules during myotubes formation.

Subunit / interactions. Homooligomer and heterooligomer. Interacts with tubulin. Interacts with TRIM63 and probably with TRIM55.

Subcellular location. Cytoplasm. Cytoskeleton. Myofibril. Sarcomere. Z line.

Tissue specificity. Specifically expressed in heart and skeletal muscle.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYV2-1	1	yes
Q9BYV2-2	2

RefSeq proteins (2): NP_115935, NP_912730* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017903	COS_domain	Domain
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR033492	Trim54_Bbox2_Zfn	Domain
IPR042752	TRIM54_RING-HC	Domain
IPR050143	TRIM/RBCC	Family

Pfam: PF00643, PF13445

UniProt features (23 total): binding site 4, strand 4, sequence conflict 2, turn 2, helix 2, zinc finger region 2, region of interest 2, chain 1, domain 1, splice variant 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3Q1D	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYV2-F1	83.71	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 149; 155; 126; 129

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 89 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_MICROTUBULE_DEPOLYMERIZATION, GRE_C, TGANTCA_AP1_C, TGACATY_UNKNOWN, CCCNNNNNNAAGWT_UNKNOWN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_PROTEIN_DEPOLYMERIZATION, GOBP_REGULATION_OF_MICROTUBULE_POLYMERIZATION_OR_DEPOLYMERIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY

GO Biological Process (5): microtubule-based process (GO:0007017), negative regulation of microtubule depolymerization (GO:0007026), signal transduction (GO:0007165), cell differentiation (GO:0030154), innate immune response (GO:0045087)

GO Molecular Function (5): microtubule binding (GO:0008017), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): cytoplasm (GO:0005737), microtubule (GO:0005874), microtubule associated complex (GO:0005875), Z disc (GO:0030018), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cellular anatomical structure	2
microtubule cytoskeleton	2
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular developmental process	1
immune response	1
defense response to symbiont	1
tubulin binding	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular anatomical structure	1
polymeric cytoskeletal fiber	1
protein-containing complex	1
I band	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1333 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM54	TTN	Q8WZ42	889
TRIM54	BBOX1	O75936	870
TRIM54	FBXO32	Q969P5	801
TRIM54	NBR1	Q14596	763
TRIM54	CAVIN4	Q5BKX8	574
TRIM54	TRIM23	P36406	542
TRIM54	MYH2	Q9UKX2	530
TRIM54	TCAP	O15273	479
TRIM54	TRAT1	Q6PIZ9	474
TRIM54	TRIM51	Q9BSJ1	453
TRIM54	SUMO2	P55855	451
TRIM54	SQSTM1	Q13501	444
TRIM54	TRIM52	Q96A61	438
TRIM54	TRIM5	Q9C035	434
TRIM54	FHL2	Q14192	433

IntAct

815 interactions, top by confidence:

A	B	Type	Score
KRT6A	TRIM54	psi-mi:“MI:0915”(physical association)	0.860
LNX1	TRIM54	psi-mi:“MI:0915”(physical association)	0.780
TRIM54	NGLY1	psi-mi:“MI:0915”(physical association)	0.780
TRIM54	LNX1	psi-mi:“MI:0915”(physical association)	0.780
TRIM54	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.740
TRIM54	CCDC102B	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	TSHZ3	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	ZNF572	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	CWF19L2	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	SH2D1B	psi-mi:“MI:0915”(physical association)	0.720
KRT6B	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	ZNF250	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	CDKN1A	psi-mi:“MI:0915”(physical association)	0.720
KRT6C	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
MFAP1	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	ZBTB16	psi-mi:“MI:0915”(physical association)	0.720
ARHGEF5	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	BYSL	psi-mi:“MI:0915”(physical association)	0.720
BYSL	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
TCEA2	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
INPP5J	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	KLHL38	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	FAM161A	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	DTX2	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
EPM2AIP1	TRIM54	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (382): TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid), TRIM54 (Two-hybrid)

ESM2 similar proteins: A0A0G2JXN2, A2AWP8, O88842, O95267, P29590, P52734, P98174, Q1LY10, Q29RM4, Q2TBA3, Q3TAA7, Q3U0J8, Q3UTZ3, Q496Y0, Q4VX76, Q568M3, Q58D15, Q5BIM1, Q5JSP0, Q5R5M3, Q5R5T1, Q5REJ9, Q5W0U4, Q68FF6, Q69Z89, Q69ZK0, Q6PFY8, Q7TNM2, Q7Z4K8, Q7Z5H3, Q7Z6J4, Q80V85, Q8BY35, Q8BZ52, Q8C190, Q8N1F8, Q8TCU6, Q8WVR3, Q96JH8, Q99N48

Diamond homologs: A0JNB0, A1Y2K1, A4IF63, A5D7F8, A5D8S5, A7A261, B0BNA1, B1V8A0, D2GXS7, D3ZQG6, F1RDG9, F7H9X2, G3X8Y1, O08641, O35179, O35180, O35964, O43125, O70277, O75382, O76041, P06241, P09769, P13406, P19706, P27446, P32793, P39688, P43603, P62484, P62993, P62994, Q02977, Q05876, Q08012, Q0CJU8, Q0U6X7, Q13588, Q1E878, Q28E95

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM54	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

83 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1330 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27299413:GAAG:G	donor_gain	1.0000
2:27299415:AGG:A	donor_loss	1.0000
2:27299417:G:GA	donor_loss	1.0000
2:27299418:T:A	donor_loss	1.0000
2:27305575:A:AG	acceptor_gain	1.0000
2:27305576:T:G	acceptor_gain	1.0000
2:27305582:A:AG	acceptor_gain	1.0000
2:27305582:AG:A	acceptor_gain	1.0000
2:27305583:G:GA	acceptor_gain	1.0000
2:27305583:GG:G	acceptor_gain	1.0000
2:27305583:GGACA:G	acceptor_gain	1.0000
2:27305765:TG:T	donor_gain	1.0000
2:27305766:GG:G	donor_gain	1.0000
2:27305788:G:GT	donor_gain	1.0000
2:27305788:G:T	donor_gain	1.0000
2:27305815:CAGGT:C	donor_loss	1.0000
2:27305816:AGGT:A	donor_loss	1.0000
2:27305817:GGTGG:G	donor_loss	1.0000
2:27305818:G:C	donor_loss	1.0000
2:27306211:AG:A	acceptor_gain	1.0000
2:27306212:GG:G	acceptor_gain	1.0000
2:27306212:GGGTC:G	acceptor_gain	1.0000
2:27306344:G:GT	donor_gain	1.0000
2:27282896:CCAGG:C	donor_loss	0.9900
2:27282897:CAGG:C	donor_loss	0.9900
2:27282898:AG:A	donor_loss	0.9900
2:27282899:GG:G	donor_loss	0.9900
2:27282900:GT:G	donor_loss	0.9900
2:27298736:CCAGG:C	donor_loss	0.9900
2:27298738:AGGT:A	donor_loss	0.9900

AlphaMissense

2354 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27282802:T:A	L24H	1.000
2:27282802:T:C	L24P	1.000
2:27282807:T:A	C26S	1.000
2:27282807:T:C	C26R	1.000
2:27282807:T:G	C26G	1.000
2:27282808:G:A	C26Y	1.000
2:27282808:G:C	C26S	1.000
2:27282808:G:T	C26F	1.000
2:27282809:C:G	C26W	1.000
2:27282816:T:A	C29S	1.000
2:27282816:T:C	C29R	1.000
2:27282817:G:A	C29Y	1.000
2:27282817:G:C	C29S	1.000
2:27282818:C:G	C29W	1.000
2:27282820:T:C	L30P	1.000
2:27282828:T:C	F33L	1.000
2:27282829:T:C	F33S	1.000
2:27282829:T:G	F33C	1.000
2:27282830:C:A	F33L	1.000
2:27282830:C:G	F33L	1.000
2:27282837:C:A	P36T	1.000
2:27282837:C:T	P36S	1.000
2:27282838:C:A	P36Q	1.000
2:27282838:C:G	P36R	1.000
2:27282838:C:T	P36L	1.000
2:27282841:T:A	V37E	1.000
2:27282847:T:A	I39N	1.000
2:27282847:T:C	I39T	1.000
2:27282850:T:A	L40Q	1.000
2:27282850:T:C	L40P	1.000

dbSNP variants (sampled 300 via entrez): RS1000315119 (2:27291597 A>G), RS1000357262 (2:27298948 C>T), RS1000389603 (2:27305406 T>G), RS1000462004 (2:27298271 C>G), RS1000777917 (2:27285370 T>C), RS1000857015 (2:27303382 T>G), RS1001134366 (2:27293638 T>C,G), RS1001267178 (2:27290248 T>C), RS1001307502 (2:27303183 A>G), RS1001362477 (2:27297398 T>A), RS1001414735 (2:27297083 A>C), RS1001719903 (2:27289932 C>T), RS1001730918 (2:27284116 G>A), RS1001905136 (2:27304747 TTAG>T), RS1001926969 (2:27301817 C>T)

Disease associations

OMIM: gene MIM:606474 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002390_350	Mean corpuscular hemoglobin	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
CGP 52608	increases reaction, affects binding	1
quinocetone	decreases expression	1
incobotulinumtoxinA	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	decreases methylation	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Thiram	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
S-Nitrosoglutathione	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TU36	HAP1 TRIM54 (-) 1	Cancer cell line	Male
CVCL_TU37	HAP1 TRIM54 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.