TRIM45

Summary

TRIM45 (tripartite motif containing 45, HGNC:19018) is a protein-coding gene on chromosome 1p13.1, encoding E3 ubiquitin-protein ligase TRIM45 (Q9H8W5). E3 ubiquitin-protein ligase that plays a role in the regulation of inflammatory response.

Enables ubiquitin protein ligase activity. Involved in negative regulation of inflammatory response; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein K48-linked ubiquitination. Located in cytosol; intercellular bridge; and nucleoplasm. Is active in cytoplasm.

Source: NCBI Gene 80263 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_025188

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19018
Approved symbol	TRIM45
Name	tripartite motif containing 45
Location	1p13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13181, RNF99
Ensembl gene	ENSG00000134253
Ensembl biotype	protein_coding
OMIM	609318
Entrez	80263

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000256649, ENST00000369461, ENST00000369464, ENST00000485032, ENST00000497970

RefSeq mRNA: 2 — MANE Select: NM_025188 NM_001145635, NM_025188

CCDS: CCDS44200, CCDS893

Canonical transcript exons

ENST00000256649 — 6 exons

Exon	Start	End
ENSE00000800599	117113359	117113485
ENSE00000800600	117115575	117115689
ENSE00000800601	117116616	117116745
ENSE00001656696	117111060	117112453
ENSE00001860154	117120714	117121749
ENSE00003787953	117118034	117118767

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 88.28.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4422 / max 54.2742, expressed in 762 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14024	1.4422	762

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	88.28	gold quality
right uterine tube	UBERON:0001302	88.27	gold quality
apex of heart	UBERON:0002098	87.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.61	gold quality
oocyte	CL:0000023	84.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.74	gold quality
muscle of leg	UBERON:0001383	84.34	gold quality
gastrocnemius	UBERON:0001388	84.11	gold quality
muscle organ	UBERON:0001630	83.12	gold quality
right atrium auricular region	UBERON:0006631	82.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.78	gold quality
cardiac atrium	UBERON:0002081	82.13	gold quality
tibialis anterior	UBERON:0001385	82.03	silver quality
oviduct epithelium	UBERON:0004804	81.20	gold quality
deltoid	UBERON:0001476	81.10	silver quality
body of pancreas	UBERON:0001150	81.02	gold quality
cervix squamous epithelium	UBERON:0006922	80.53	gold quality
biceps brachii	UBERON:0001507	80.52	gold quality
quadriceps femoris	UBERON:0001377	80.22	silver quality
fallopian tube	UBERON:0003889	80.22	gold quality
body of uterus	UBERON:0009853	80.09	gold quality
skeletal muscle tissue	UBERON:0001134	79.95	gold quality
vastus lateralis	UBERON:0001379	79.86	silver quality
muscle tissue	UBERON:0002385	79.58	gold quality
thyroid gland	UBERON:0002046	79.40	gold quality
ganglionic eminence	UBERON:0004023	79.31	gold quality
pituitary gland	UBERON:0000007	79.19	gold quality
left lobe of thyroid gland	UBERON:0001120	79.12	gold quality
embryo	UBERON:0000922	79.11	gold quality
heart left ventricle	UBERON:0002084	78.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting TRIM45, 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-4776-3P	100.00	68.73	1340
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-6770-5P	98.97	66.76	1853

Literature-anchored findings (GeneRIF, showing 7)

• TRIM45 may act as a new transcriptional repressor in mitogen-activated protein kinase signaling pathway (PMID:15351693)
• These findings suggest that TRIM45 acts as a repressor for the NF-kappaB signal and regulates cell growth. (PMID:22634006)
• The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway. (PMID:24681954)
• These findings suggest that TRIM45 is a novel tumor suppressor that stabilizes and activates p53 in glioma. (PMID:28542145)
• TRIM45 Suppresses the Development of Non-small Cell Lung Cancer. (PMID:31663468)
• TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy. (PMID:38037161)
• TRIM45 facilitates NASH-progressed HCC by promoting fatty acid synthesis via catalyzing FABP5 ubiquitylation. (PMID:38755308)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim45	ENSDARG00000076781
mus_musculus	Trim45	ENSMUSG00000033233
rattus_norvegicus	Trim45	ENSRNOG00000015347

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), 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), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

E3 ubiquitin-protein ligase TRIM45 — Q9H8W5 (reviewed: Q9H8W5)

Alternative names: RING finger protein 99

All UniProt accessions (4): Q9H8W5, H0YCA7, Q5T2K3, S4R407

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that plays a role in the regulation of inflammatory response. Mechanistically, mediates the ‘Lys-48’-linked polyubiquitination of TAB2, a regulatory protein of the kinase TAK1, leading to its degradation via the proteasomal pathway and inhibition of the TLR-mediated inflammatory immune response. May act as a transcriptional repressor in mitogen-activated protein kinase signaling pathway.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in skeletal muscle, brain, heart and pancreas.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H8W5-1	1	yes
Q9H8W5-2	2

RefSeq proteins (2): NP_001139107, NP_079464* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001298	Filamin/ABP280_rpt	Repeat
IPR001841	Znf_RING	Domain
IPR003649	Bbox_C	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR017868	Filamin/ABP280_rpt-like	Repeat
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR047153	TRIM45/56/19-like	Family

Pfam: PF00630, PF00643, PF13445

UniProt features (32 total): strand 9, binding site 8, sequence variant 4, zinc finger region 3, mutagenesis site 2, turn 2, chain 1, repeat 1, splice variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DS4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H8W5-F1	80.27	0.48

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 (8): 191; 194; 214; 219; 135; 138; 158; 162

Mutagenesis-validated functional residues (2):

Position	Phenotype
94	loss of ubiquitination activity; when associated with a-97.
97	loss of ubiquitination activity; when associated with a-94.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 116 (showing top): GOBP_SKELETAL_SYSTEM_DEVELOPMENT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, FISCHER_G1_S_CELL_CYCLE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_BONE_DEVELOPMENT, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, FISCHER_DREAM_TARGETS, WONG_MITOCHONDRIA_GENE_MODULE, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE

GO Biological Process (5): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of inflammatory response (GO:0050728), bone development (GO:0060348), protein K48-linked ubiquitination (GO:0070936), inflammatory response (GO:0006954)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), intercellular bridge (GO:0045171), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
skeletal system development	1
animal organ development	1
protein polyubiquitination	1
defense response	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

501 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM45	SORBS1	Q9BX66	908
TRIM45	STAC	Q99469	907
TRIM45	FCHSD2	O94868	881
TRIM45	SPART	Q8N0X7	880
TRIM45	KIR2DL1	P43626	851
TRIM45	TRAT1	Q6PIZ9	832
TRIM45	KIR2DL4	P78400	806
TRIM45	TRIM41	Q8WV44	778
TRIM45	KIR3DL1	P43629	773
TRIM45	HLA-C	P04222	767
TRIM45	KIR3DL3	Q8N743	767
TRIM45	TMLHE	Q9NVH6	765
TRIM45	CDK2	P24941	746
TRIM45	KIR3DL2	P43630	723
TRIM45	BBOX1	O75936	713

IntAct

9 interactions, top by confidence:

A	B	Type	Score
MGME1	WDHD1	psi-mi:“MI:0914”(association)	0.530
AARSD1	APAF1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
STK25	ACACB	psi-mi:“MI:0914”(association)	0.350
GABARAPL2		psi-mi:“MI:0914”(association)	0.350
AARSD1	MAP3K7	psi-mi:“MI:0914”(association)	0.350
TRIM45	RABEP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (47): TRIM45 (Affinity Capture-MS), TRIM45 (Affinity Capture-MS), TRIM45 (Affinity Capture-Western), TP53 (Affinity Capture-Western), TRIM45 (Two-hybrid), TRIM45 (Two-hybrid), TRIM45 (Two-hybrid), TRIM45 (Two-hybrid), TRIM45 (Two-hybrid), TRIM45 (Two-hybrid), ZMYND19 (Two-hybrid), ENTHD2 (Two-hybrid), TRIM45 (Reconstituted Complex), TRIM45 (Affinity Capture-RNA), COG4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A2AWP8, A2RRH5, C9J798, O43374, O70277, O95294, P04629, P59926, Q0GA42, Q13368, Q14318, Q16512, Q29RM4, Q2HY40, Q2T9P3, Q2TBA3, Q5BIM1, Q5M7W1, Q5R5M3, Q5R811, Q5T7P8, Q5XIS9, Q62746, Q6PFQ7, Q6PFY8, Q7TNM2, Q7TP90, Q7Z4K8, Q8BG60, Q8BHT7, Q8BQC3, Q8C6N3, Q8CIW5, Q8IZ69, Q8NCT1, Q920N2, Q92546, Q925B4

Diamond homologs: A4IF63, A5D7D1, D2GXS7, D3ZHA0, D3ZHV2, D3ZQG6, D3ZVM4, E1BJS7, E7FAM5, F6QEU4, F7H9X2, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O97592, P05094, P05095, P11277, P11530, P11531, P11532, P11533, P12814, P15508, P18091, P20111, P21333, P30427, P35609, P46939, P57780, Q00963, Q01082, Q03001

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM45	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1509 predictions. Top by Δscore:

Variant	Effect	Δscore
1:117113501:C:CT	acceptor_gain	1.0000
1:117115569:TCTTA:T	donor_loss	1.0000
1:117115570:CTTA:C	donor_loss	1.0000
1:117115571:TTAC:T	donor_loss	1.0000
1:117115572:TACC:T	donor_loss	1.0000
1:117115573:A:C	donor_loss	1.0000
1:117115574:C:A	donor_loss	1.0000
1:117115685:CTGGG:C	acceptor_gain	1.0000
1:117115686:TGGG:T	acceptor_gain	1.0000
1:117115690:C:CC	acceptor_gain	1.0000
1:117115694:A:AC	acceptor_gain	1.0000
1:117116628:T:C	donor_gain	1.0000
1:117118764:CCGC:C	acceptor_gain	1.0000
1:117118765:CGC:C	acceptor_gain	1.0000
1:117118765:CGCC:C	acceptor_gain	1.0000
1:117118767:CCT:C	acceptor_loss	1.0000
1:117118768:C:CC	acceptor_gain	1.0000
1:117118768:CTAGG:C	acceptor_loss	1.0000
1:117118769:T:A	acceptor_loss	1.0000
1:117118786:A:T	acceptor_gain	1.0000
1:117120716:ATGAG:A	donor_gain	1.0000
1:117120777:T:TA	donor_gain	1.0000
1:117120778:C:A	donor_gain	1.0000
1:117121640:T:TA	donor_gain	1.0000
1:117113353:CCTTA:C	donor_loss	0.9900
1:117113354:CTTA:C	donor_loss	0.9900
1:117113355:TTACC:T	donor_loss	0.9900
1:117113356:TA:T	donor_loss	0.9900
1:117113357:ACCTG:A	donor_loss	0.9900
1:117113358:C:CT	donor_loss	0.9900

AlphaMissense

3798 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:117113382:C:G	C524S	0.982
1:117113383:A:T	C524S	0.982
1:117113414:G:C	F513L	0.981
1:117113414:G:T	F513L	0.981
1:117113416:A:G	F513L	0.981
1:117112438:C:G	C537S	0.980
1:117112439:A:T	C537S	0.980
1:117113383:A:G	C524R	0.980
1:117113429:A:C	F508L	0.979
1:117113429:A:T	F508L	0.979
1:117113431:A:G	F508L	0.979
1:117118266:G:C	F330L	0.979
1:117118266:G:T	F330L	0.979
1:117118268:A:G	F330L	0.979
1:117113412:C:G	C514S	0.977
1:117113413:A:T	C514S	0.977
1:117113413:A:G	C514R	0.975
1:117113420:G:C	C511W	0.973
1:117112394:A:G	C552R	0.971
1:117113422:A:G	C511R	0.971
1:117113411:G:C	C514W	0.970
1:117118134:G:C	F374L	0.970
1:117118134:G:T	F374L	0.970
1:117118136:A:G	F374L	0.970
1:117113376:C:G	C526S	0.969
1:117113377:A:T	C526S	0.969
1:117112393:C:G	C552S	0.968
1:117112394:A:T	C552S	0.968
1:117112439:A:G	C537R	0.968
1:117113377:A:G	C526R	0.967

dbSNP variants (sampled 300 via entrez): RS1000093782 (1:117112350 A>C,G,T), RS1000108353 (1:117112882 GAC>G), RS1000381225 (1:117125269 C>T), RS1000399040 (1:117119785 A>C,G,T), RS1000407402 (1:117125571 C>A,G,T), RS1000412459 (1:117124979 G>GA), RS1001082581 (1:117114281 T>A,C), RS1001099099 (1:117113672 T>C), RS1001471554 (1:117118962 G>T), RS1001539518 (1:117113149 A>C), RS1001773883 (1:117125462 A>G), RS1001928210 (1:117125663 G>C), RS1002467935 (1:117120587 T>C), RS1002594420 (1:117114751 T>TA), RS1002610719 (1:117110652 A>G)

Disease associations

OMIM: gene MIM:609318 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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
Valproic Acid	affects expression, increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression	2
Nickel	decreases expression	2
pirinixic acid	decreases expression, increases activity, affects binding	1
sodium arsenite	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Cisplatin	increases expression, affects cotreatment	1
Estradiol	decreases expression	1
Gallic Acid	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Vincristine	decreases expression	1
Cyclosporine	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Antirheumatic Agents	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TU28	HAP1 TRIM45 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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