TRIM60

Summary

TRIM60 (tripartite motif containing 60, HGNC:21162) is a protein-coding gene on chromosome 4q32.3, encoding Tripartite motif-containing protein 60 (Q495X7). E3 SUMO-protein ligase that mediates SUMOylation of TAB2 leading to inhibition of NF-kappa-B and MAPK pathways by suppressing the TRAF6/TAB2/TAK1 complex.

The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. Pseudogenes of this gene are located on more than six chromosomes including chromosome 4. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 166655 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_152620

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21162
Approved symbol	TRIM60
Name	tripartite motif containing 60
Location	4q32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35882
Ensembl gene	ENSG00000176979
Ensembl biotype	protein_coding
OMIM	619416
Entrez	166655

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000341062, ENST00000507119, ENST00000508504, ENST00000512596, ENST00000647760

RefSeq mRNA: 2 — MANE Select: NM_152620 NM_001258025, NM_152620

CCDS: CCDS3808

Canonical transcript exons

ENST00000512596 — 3 exons

Exon	Start	End
ENSE00002055276	165039201	165039252
ENSE00002076607	165031999	165032112
ENSE00003848655	165040069	165041749

Expression profiles

Bgee: expression breadth tissue_specific, 9 present calls, max score 86.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0589 / max 25.7703, expressed in 10 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50430	0.0274	6
50431	0.0200	6
50429	0.0115	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.90	gold quality
placenta	UBERON:0001987	68.45	gold quality
testis	UBERON:0000473	51.18	gold quality
right testis	UBERON:0004534	50.88	gold quality
left testis	UBERON:0004533	49.75	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
apex of heart	UBERON:0002098	35.04	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
right uterine tube	UBERON:0001302	32.78	gold quality
mucosa of stomach	UBERON:0001199	32.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
monocyte	CL:0000576	30.87	silver quality
leukocyte	CL:0000738	30.57	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.21	gold quality
liver	UBERON:0002107	28.76	gold quality
tonsil	UBERON:0002372	28.67	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.41	gold quality
calcaneal tendon	UBERON:0003701	26.65	gold quality
right coronary artery	UBERON:0001625	26.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting TRIM60, 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-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-198	98.70	67.32	920
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-6501-5P	97.41	68.24	712
HSA-MIR-4794	96.47	65.53	1063
HSA-MIR-664A-5P	95.84	64.93	949
HSA-MIR-4431	90.07	69.53	39

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim60	ENSMUSG00000053490

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), TRIM54 (ENSG00000138100), 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)

Protein

Protein identifiers

Tripartite motif-containing protein 60 — Q495X7 (reviewed: Q495X7)

Alternative names: RING finger protein 129, RING finger protein 33

All UniProt accessions (2): D6RAS2, Q495X7

UniProt curated annotations — full annotation on UniProt →

Function. E3 SUMO-protein ligase that mediates SUMOylation of TAB2 leading to inhibition of NF-kappa-B and MAPK pathways by suppressing the TRAF6/TAB2/TAK1 complex.

Similarity. Belongs to the TRIM/RBCC family.

RefSeq proteins (2): NP_001244954, NP_689833* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR035786	SPRY/PRY_TRIM60	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF13765, PF15227

UniProt features (10 total): binding site 4, zinc finger region 2, chain 1, domain 1, coiled-coil region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q495X7-F1	86.05	0.52

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): 97; 100; 119; 125

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): chr4q32, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_SUMO_TRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOMF_SUMO_LIGASE_ACTIVITY, HMGA1_TARGET_GENES, MIR5582_3P, MIR9902, MIR376A_3P_MIR376B_3P

GO Biological Process (6): regulation of gene expression (GO:0010468), innate immune response (GO:0045087), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), canonical NF-kappaB signal transduction (GO:0007249), non-canonical NF-kappaB signal transduction (GO:0038061), protein K63-linked ubiquitination (GO:0070534)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), SUMO-ubiquitin ligase activity (GO:0140082), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular signaling cassette	2
gene expression	1
regulation of macromolecule biosynthetic process	1
immune response	1
defense response to symbiont	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
protein polyubiquitination	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
SUMO ligase activity	1
binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM60	KIF3B	O15066	777
TRIM60	KIF3A	Q9Y496	596
TRIM60	ZNF736	B4DX44	594
TRIM60	ZNF679	Q8IYX0	499
TRIM60	OR52E4	Q8NGH9	463
TRIM60	BBOX1	O75936	456
TRIM60	FAM218A	Q96MZ4	446
TRIM60	CALU	O43852	431
TRIM60	TRIM42	Q8IWZ5	418
TRIM60	ZNF680	Q8NEM1	412
TRIM60	SPIDR	Q14159	407
TRIM60	TRAT1	Q6PIZ9	391
TRIM60	HGSNAT	Q68CP4	387
TRIM60	FNTA	P49354	386
TRIM60	HOOK3	Q86VS8	381

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TRIM60	LNX1	psi-mi:“MI:0915”(physical association)	0.560
TRIM60	LNX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): TRIM60 (Affinity Capture-MS), TRIM60 (Two-hybrid), TRIM60 (Reconstituted Complex)

ESM2 similar proteins: A6NK02, A6NLU0, D4ABM4, F8VTS6, O00635, O19085, O77666, P14373, P15533, P62603, P86448, P86449, Q12899, Q2T9Z0, Q3UWZ0, Q495X7, Q58DK8, Q5BK82, Q5D7H7, Q5D7I6, Q5E9G4, Q5RBG2, Q5SZ99, Q5TM55, Q62158, Q62191, Q640S6, Q6AZZ1, Q6PGR9, Q7TPM3, Q7YR32, Q7YR33, Q7YR34, Q7YRV4, Q80X56, Q86WT6, Q8BVP1, Q8K243, Q8N7C3, Q8N9V2

Diamond homologs: A0JN74, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NK02, A6NLI5, B1H278, C9J1S8, K7N6K2, O00635, O15553, O19085, O77666, P0CI25, P0CI26, P14373, P15533, P18892, P19474, Q02084, Q0PF16, Q12899, Q13410, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q1XHU0, Q2T9Z0, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3UWZ0, Q3ZEE5, Q495X7, Q587N6, Q587N7, Q58DK8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM60	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

342 predictions. Top by Δscore:

Variant	Effect	Δscore
4:165032111:AGG:A	donor_loss	1.0000
4:165032112:GGTA:G	donor_loss	1.0000
4:165032113:G:GG	donor_gain	0.9900
4:165032114:T:G	donor_loss	0.9900
4:165039232:G:GA	donor_gain	0.9900
4:165040067:A:AG	acceptor_gain	0.9900
4:165040068:G:GG	acceptor_gain	0.9900
4:165040068:GCTC:G	acceptor_gain	0.9900
4:165040067:AGCTC:A	acceptor_gain	0.9800
4:165040068:GCTCG:G	acceptor_gain	0.9800
4:165039231:T:TA	donor_gain	0.9700
4:165040063:TCGCA:T	acceptor_loss	0.9700
4:165040064:CGCA:C	acceptor_loss	0.9700
4:165040065:GCA:G	acceptor_loss	0.9700
4:165040066:CA:C	acceptor_loss	0.9700
4:165040067:A:AT	acceptor_loss	0.9700
4:165039233:G:GG	donor_gain	0.9400
4:165039544:A:AG	donor_gain	0.9400
4:165040068:GC:G	acceptor_gain	0.9400
4:165040068:GCT:G	acceptor_gain	0.9400
4:165032111:AG:A	donor_gain	0.9200
4:165032112:GG:G	donor_gain	0.9200
4:165032109:CCAG:C	donor_gain	0.9100
4:165032108:TCCAG:T	donor_gain	0.8800
4:165032110:CAG:C	donor_gain	0.8700
4:165039230:G:GT	donor_gain	0.8700
4:165039194:ATTGC:A	acceptor_loss	0.8600
4:165039195:TTGCA:T	acceptor_loss	0.8600
4:165039196:TGCA:T	acceptor_loss	0.8600
4:165039197:GCAGG:G	acceptor_loss	0.8600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS10000216 (4:165033713 T>C), RS1000027239 (4:165031517 G>A,C), RS1000042211 (4:165031441 T>C), RS1000133098 (4:165032025 G>A,C), RS1000782303 (4:165035972 C>T), RS1000905941 (4:165032795 C>T), RS10009883 (4:165032847 A>C), RS1001013765 (4:165030338 G>C), RS1001359861 (4:165032583 C>A,G), RS1001393410 (4:165038492 C>G), RS1001746043 (4:165038786 A>G), RS1002140510 (4:165034826 C>A), RS1002184014 (4:165039451 C>A,T), RS1002308780 (4:165034266 C>A), RS1002340279 (4:165039833 G>A)

Disease associations

OMIM: gene MIM:619416 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007830_1	Anti-thyroid peroxidase (TPOAb) levels in Hashimoto’s thyroiditis	5.000000e-07
GCST007851_1	Anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TgAb) levels in Hashimoto’s thyroiditis	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
terbufos	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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