TRIM28

Summary

TRIM28 (tripartite motif containing 28, HGNC:16384) is a protein-coding gene on chromosome 19q13.43, encoding Transcription intermediary factor 1-beta (Q13263). Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). It is a selective cancer dependency (DepMap: 18.0% of cell lines).

The protein encoded by this gene mediates transcriptional control by interaction with the Kruppel-associated box repression domain found in many transcription factors. The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of the tripartite motif family. This tripartite motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region.

Source: NCBI Gene 10155 — RefSeq curated summary.

At a glance

• Gene–disease (curated): childhood kidney Wilms tumor (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 324 total — 10 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 18.0% of screened cell lines
• MANE Select transcript: NM_005762

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16384
Approved symbol	TRIM28
Name	tripartite motif containing 28
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	TIF1B, KAP1, TF1B, RNF96, PPP1R157, KAP-1, TIF1-beta, TIF1beta
Ensembl gene	ENSG00000130726
Ensembl biotype	protein_coding
OMIM	601742
Entrez	10155

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 19 protein_coding, 9 retained_intron

ENST00000253024, ENST00000341753, ENST00000593582, ENST00000594806, ENST00000595028, ENST00000595974, ENST00000597136, ENST00000597172, ENST00000597423, ENST00000597618, ENST00000597968, ENST00000597995, ENST00000598355, ENST00000600840, ENST00000601150, ENST00000887640, ENST00000887641, ENST00000913372, ENST00000913373, ENST00000913374, ENST00000913375, ENST00000913376, ENST00000913377, ENST00000913378, ENST00000950724, ENST00000950725, ENST00000950726, ENST00000950727

RefSeq mRNA: 1 — MANE Select: NM_005762 NM_005762

CCDS: CCDS12985

Canonical transcript exons

ENST00000253024 — 17 exons

Exon	Start	End
ENSE00000655818	58549331	58549650
ENSE00000655819	58548988	58549240
ENSE00000655828	58547376	58547511
ENSE00001391650	58550377	58550715
ENSE00001469551	58544064	58545097
ENSE00003513051	58548862	58548910
ENSE00003515727	58545425	58545537
ENSE00003530508	58549949	58550035
ENSE00003542576	58547792	58547906
ENSE00003563013	58547597	58547713
ENSE00003583389	58550147	58550284
ENSE00003587053	58549737	58549860
ENSE00003589433	58548486	58548592
ENSE00003649240	58548740	58548776
ENSE00003654842	58548294	58548408
ENSE00003681333	58548034	58548180
ENSE00003785969	58545764	58545896

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 129.4845 / max 866.6649, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177858	125.7829	1826
177856	2.3829	1277
177860	0.6439	345
177859	0.6183	338
177857	0.0564	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.72	gold quality
right testis	UBERON:0004534	99.72	gold quality
ventricular zone	UBERON:0003053	99.71	gold quality
embryo	UBERON:0000922	99.66	gold quality
ganglionic eminence	UBERON:0004023	99.66	gold quality
cortical plate	UBERON:0005343	99.55	gold quality
stromal cell of endometrium	CL:0002255	99.47	gold quality
left ovary	UBERON:0002119	99.42	gold quality
right ovary	UBERON:0002118	99.40	gold quality
body of uterus	UBERON:0009853	99.39	gold quality
ovary	UBERON:0000992	99.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.36	gold quality
right uterine tube	UBERON:0001302	99.34	gold quality
right lobe of thyroid gland	UBERON:0001119	99.31	gold quality
left uterine tube	UBERON:0001303	99.30	gold quality
fundus of stomach	UBERON:0001160	99.29	gold quality
cerebellum	UBERON:0002037	99.29	gold quality
fallopian tube	UBERON:0003889	99.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.29	gold quality
cerebellar cortex	UBERON:0002129	99.28	gold quality
cerebellar hemisphere	UBERON:0002245	99.28	gold quality
body of pancreas	UBERON:0001150	99.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.27	gold quality
left lobe of thyroid gland	UBERON:0001120	99.24	gold quality
thyroid gland	UBERON:0002046	99.23	gold quality
prostate gland	UBERON:0002367	99.23	gold quality
lymph node	UBERON:0000029	99.22	gold quality
body of stomach	UBERON:0001161	99.22	gold quality
endocervix	UBERON:0000458	99.21	gold quality
myometrium	UBERON:0001296	99.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.24

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
ALDOA	Repression
E2F3	Repression
E2F4	Repression
ID1	Unknown
IFNG
VIM
ZNF274	Unknown

Upstream regulators (CollecTRI, top): IRF1, NFKB2, NFKB, NKX3-1, NR2C1, NR2C2, NSD2, RELA, STAT3, TBX15, TP53, ZKSCAN7, ZNF250, ZNF256, ZNF316, ZNF350, ZNF436, ZNF571

miRNA regulators (miRDB)

38 targeting TRIM28, 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-4481	100.00	66.42	1669
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-637	97.91	64.05	1517

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Purified RINGs, including KAP-1, self-assemble into supramolecular structures in vitro that resemble those they form in cells. (PMID:12438698)
• interacts with BBLF2/3 to provide an origin-tethering function for the EBV replication complex (PMID:15596820)
• ARF may regulate p53 acetylation and stability in part by inhibiting KAP1-MDM2 binding (PMID:16107876)
• A novel Fes-KAP-1 interaction is reported, suggesting a dual role for KAP-1 as both a Fes activator and downstream effector. (PMID:16792528)
• KAP1 functions to coordinate activities that dynamically regulate changes in histone modifications and deposition of HP1 to establish a de novo microenvironment of heterochromatin, which is required for repression of gene transcription by KRAB-zfps. (PMID:16954381)
• Dox-induced decrease in KAP1 sumoylation is essential for Dox to induce p21 expression and subsequent cell growth inhibition in MCF-7 cells (PMID:17079232)
• DNA damage-induced phosphorylation of the protein 1 (KAP1), providing a link between chromatin-mediated transcriptional repression and the recognition/repair of DNA. (PMID:17178852)
• Limited proteolysis, mass spectrometry and N-terminal sequence analyses suggest that a core complex comprises the entire RBCC domain of KAP-1 and the AB box of the KRAB domain rendering it resistant to proteolysis. (PMID:17512541)
• Expression of KRAB-box zinc finger genes may be controlled via an auto-regulatory mechanism involving KAP1. (PMID:17542650)
• KAP1 contributes to the negative regulation of E2F1 and may serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of pRb (PMID:17704056)
• a novel role for ATM that selectively stimulates KAP1 Ser-824 phosphorylation to repress its sumoylation, leading to the de-repression of expression of a subset of genes involved in promoting cell cycle control and apoptosis (PMID:17942393)
• These findings suggest that BMZF3 is a transcriptional repressor induced by GDNF that plays a role in cell proliferation. (PMID:18060868)
• KAP1 interacts with STAT1 and regulates IFN/STAT1-mediated IRF-1 gene expression in collaboration with HDACs. (PMID:18381204)
• role as an intramolecular small ubiquitin-like modifier E3 ligase for transcriptional silencing. (PMID:18488044)
• modulation of HP1beta-TIF1beta interaction through the phosphorylation/de-phosphorylation of TIF1beta/Ser473 may constitute a molecular switch that regulates the expression of particular genes (PMID:18590578)
• The histone subcode: poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 control cell differentiation by regulating the transcriptional intermediary factor TIF1beta and the heterochromatin protein HP1alpha (PMID:18676401)
• KRAB/KAP1 regulation is fully functional within the context of episomal DNA (PMID:19279087)
• TIF1beta is an important coactivator of NGFI-B-dependent transcription. (PMID:19321449)
• Data show that cellular transcriptional repressor KAP-1 plays a role in regulating KSHV latency, and viral protein kinase modulates the chromatin remodeling function of this repressor. (PMID:19584288)
• Data show that the transcriptional corepressor KAP1 can inactivate the kinetochore. (PMID:19656847)
• The KRAB-O protein can simultaneously bind KAP1 and SRY in a noncompetitive but also noncooperative manner. (PMID:19850934)
• Overexpression of KAP1 is associated with peritoneal carcinomatosis in gastric cancer. (PMID:19898899)
• Results not only show that HDAC10 regulates melanogenesis but also demonstrate that the transcriptional activities of Pax3 and KAP1 are intimately linked to their acetylation status. (PMID:20032463)
• 53BP1 amplifies Mre11-NBS1 accumulation at late-repairing DSBs, concentrating active ATM and leading to robust, localized pKAP-1. (PMID:20081839)
• KRAB/KAP1 recruitment induces long-range repression through the spread of heterochromatin. (PMID:20221260)
• posit a mechanism whereby the combined actions of PP1alpha and PP1beta cause dephosphorylation of KAP1 at Ser(824) and assure its SUMOylation (PMID:20424263)
• Kap1 reduces ERBB4 transcription and either directly or indirectly modulates the expression of genes that are themselves regulated by ErbB4. (PMID:20858735)
• analysis of a KRAB domain-containing ZNF (ZNF274) that is involved in recruitment of the KAP1 and SETDB1 to specific regions of the human genome (PMID:21170338)
• The phosphorylation of KAP1 at S284 by ATM regulated the initial increase in PML NB number following the induction of DNA double breaks by etotoside. (PMID:21228624)
• analysis of binding of NPM1, TRIM28, and YB-1 to the Mf2 domain of IRF-1 (PMID:21245151)
• Deletion of the RBCC domain abolished KAP1 binding to the 3’ exons of zinc finger genes but KAP1 binding to promoter regions was unaffected. (PMID:21343339)
• KAP1 [KRAB (Kruppel-associated box)-associated protein 1)] is a novel Nrf2-NT-interacting protein which regulates susceptibility to oxidative stress. (PMID:21382013)
• KAP1 protein: an enigmatic master regulator of the genome. (PMID:21652716)
• KAP1 inhibits HIV-1 integration via binding to acetylated HIV-1 integrase. (PMID:21669397)
• high levels of gene activity in the genomic environment and the pre-deposition of repressive histone marks within a gene increase its susceptibility to KRAB/KAP1-mediated repression (PMID:21791101)
• Expression of MAGE I proteins, MAGE-A3 or MAGE-C2, relieved repression of a reporter gene by ZNF382 and MAGE I expression relieved KAP1 mediated ID1 repression. (PMID:21876767)
• HP1-dependent regulation of KAP1 influences DNA repair in heterochromatin. (PMID:22205726)
• The authors devised a novel proteomic strategy for systematic identification of proteins dephosphorylated by PP4C and identified KRAB-domain-associated protein 1 (KAP-1) as a substrate. (PMID:22491012)
• KAP1 Ser-473 phosphorylation was required for efficient DNA repair and cell survival in response to DNA damage. (PMID:22496453)
• Anti-TRIM28 is a new dermatomyositis autoantibody associated with a mild form of myopathy. (PMID:22513056)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000051804
danio_rerio	trim33l	ENSDARG00000086126
mus_musculus	Trim28	ENSMUSG00000005566
rattus_norvegicus	Trim28	ENSRNOG00000027487

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), 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), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

Transcription intermediary factor 1-beta — Q13263 (reviewed: Q13263)

Alternative names: E3 SUMO-protein ligase TRIM28, KRAB-associated protein 1, KRAB-interacting protein 1, Nuclear corepressor KAP-1, RING finger protein 96, RING-type E3 ubiquitin transferase TIF1-beta, Tripartite motif-containing protein 28

All UniProt accessions (5): Q13263, M0QZE6, M0R0K9, M0R2I3, M0R3C0

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at ‘Lys-9’ (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 ‘Lys-9 and ‘Lys-14’ acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway. Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3’-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions. (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1.

Subunit / interactions. Interacts with SETX. Oligomer; the RBCC domain homotrimerizes and interacts with one molecule of KRAB to form the KRAB-KAP1 corepressor complex. Binding to a KRAB domain is an absolute requirement for silencing gene expression. Interacts with CEBPB and NR3C1. Interacts with a number of KRAB-ZFP proteins including ZNF10, ZFP53, ZFP68, ZNF382 and ZNF256. Interacts with NCOR1, NR3C1 and CHD3. Interacts with CEBPB (via the RING-type and PHD-type zinc fingers). Component of a ternary complex that includes TRIM28, a HP1 protein (CBX1, CBX3 OR CBX5), a KRAB domain-containing protein, and DNA. Interacts with CBX5 (via the PxVxL motif); the interaction occurs in interphase nuclei and competes for binding POGZ. Interacts with POGZ; the interaction competes for interaction with CBX5. Interacts with SETDB1; the interaction is enhanced by KAP1 sumoylation, stimulates SETDB1 histone methyltransferase activity and gene silencing. Interacts (via the PHD-type zinc finger) with UBE2I; the interaction is required for sumoylation and repressor activity. Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor and DNA damage responses. Interacts directly with ERBB4; the interaction represses ERBB4-mediated transcription activity. Interacts with MDM2; the interaction contributes to p53/TP53 inactivation. Component of the TRIM28/KAP1-MDM2-p53/TP53; involved in regulating p53/TP53 stabilization and activity. Interacts (via the leucine zipper alpha helical coiled-coil) with E2F1 (central region); the interaction inhibits E2F1 acetylation and transcriptional activity. Interacts with PPP1CA; the interaction dephosphorylates TRIM28 at Ser-824 and forms a complex at the p21 promoter site. Interacts with PPP1CB; the interaction is weak but is increased on dephosphorylation at Ser-824. Interacts with FES/FPS. Interacts with SMARCAD1. Interacts with, and sumoylates IRF7. Interacts with MAGEC2. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with AICDA. Interacts (via the RBCC domain) with KOX1 (via the KRAB domain), ZNF268 (via the KRAB domain) and ZNF300 (via the KRAB domain); the interactions increase KOX1, ZNF268 and ZNF300 nuclear localization activities. The large PER complex involved in the histone methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex. Interacts with isoform 2 of ZFP90. Forms a complex with FOXP3 in the presence of isoform 2 of ZFP90. Interacts with NR4A3; the interactions potentiates NR4A3 activity on NurRE promoter. Interacts (unphosphorylated or phosphorylated form) with ZBTB1 (via BTB domain). Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1. Interacts with ATRX. Forms a complex with ATRX, SETDB1 and ZNF274. Interacts with ZFP568; the interaction mediates ZFP568 transcriptional repression activity. Interacts with RRP1B. Interacts with CRY1. Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression. Interacts with CYREN (via XLF motif). Interacts with TRIM17; this interaction prevents TRIM28 activity. Interacts with ZNF746. Interacts with PHF13. Interacts with ZNF354C. Interacts with ZNF432; the interaction is independent of PARP1. (Microbial infection) Interacts with herpes virus 8 protein LANA1; this interaction facilitates establishment of viral latency.

Subcellular location. Nucleus.

Tissue specificity. Expressed in all tissues tested including spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.

Post-translational modifications. ATM-induced phosphorylation on Ser-824 represses sumoylation leading to the de-repression of expression of a subset of genes involved in cell cycle control and apoptosis in response to genotoxic stress. Dephosphorylation by the phosphatases, PPP1CA and PP1CB forms, allows sumoylation and expression of TRIM28 target genes. Sumoylation/desumoylation events regulate TRIM28-mediated transcriptional repression. Sumoylation is required for interaction with CHD3 and SETDB1 and the corepressor activity. Represses and is repressed by Ser-824 phosphorylation. Enhances the TRIM28 corepressor activity, inhibiting transcriptional activity of a number of genes including GADD45A and CDKN1A/p21. Lys-554, Lys-779 and Lys-804 are the major sites of sumoylation. In response to Dox-induced DNA damage, enhanced phosphorylation on Ser-824 prevents sumoylation and allows de-repression of CDKN1A/p21. Auto-ubiquitinated; enhanced by MAGEA2 and MAGEC2. Citrullinated by PADI4. ADP-ribosylated by SIRT6, promoting TRIM28/KAP1 interaction with CBX5, thereby contributing to the packaging of LINE-1 retrotransposon elements into transcriptionally repressive heterochromatin.

Disease relevance. Wilms tumor 7 (WT7) [MIM:621332] A pediatric malignancy of kidney, and the most common childhood abdominal malignancy. It is caused by the uncontrolled multiplication of renal stem, stromal, and epithelial cells. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. The HP1 box is both necessary and sufficient for HP1 binding. The PHD-type zinc finger enhances CEBPB transcriptional activity. The PHD-type zinc finger, the HP1 box and the bromo domain, function together to assemble the machinery required for repression of KRAB domain-containing proteins. Acts as an intramolecular SUMO E3 ligase for autosumoylation of bromodomain. The RING-finger-B Box-coiled-coil/tripartite motif (RBCC/TRIM motif) is required for interaction with the KRAB domain of KRAB-zinc finger proteins. Binds four zinc ions per molecule. The RING finger and the N-terminal of the leucine zipper alpha helical coiled-coil region of RBCC are required for oligomerization. Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.

Pathway. Protein modification; protein sumoylation.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13263-1	1	yes
Q13263-2	2

RefSeq proteins (1): NP_005753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001487	Bromodomain	Domain
IPR001841	Znf_RING	Domain
IPR001965	Znf_PHD	Domain
IPR003649	Bbox_C	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR037373	KAP1	Domain
IPR042713	TIF1beta_RING-HC	Domain
IPR047058	TIF1b_Bbox2_Znf	Domain
IPR047059	TIF1b_Bbox1_Znf	Domain

Pfam: PF00628, PF00643, PF14634

UniProt features (166 total): modified residue 34, cross-link 29, mutagenesis site 23, strand 19, helix 14, region of interest 9, sequence variant 9, turn 8, binding site 8, zinc finger region 4, compositionally biased region 3, initiator methionine 1, chain 1, sequence conflict 1, short sequence motif 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9OSC	X-RAY DIFFRACTION	1.77
2YVR	X-RAY DIFFRACTION	1.8
9CDW	X-RAY DIFFRACTION	2.4
7Z36	X-RAY DIFFRACTION	2.8
6QAJ	X-RAY DIFFRACTION	2.9
6QU1	X-RAY DIFFRACTION	3.7
6H3A	X-RAY DIFFRACTION	5.5
1FP0	SOLUTION NMR
2RO1	SOLUTION NMR
6I9H	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13263-F1	67.59	0.26

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): 153; 156; 177; 181; 209; 212; 232; 237

Post-translational modifications (63): 2, 19, 26, 50, 138, 266, 304, 340, 377, 417, 437, 439, 453, 470, 471, 472, 473, 479, 489, 498 …

Mutagenesis-validated functional residues (23):

Position	Phenotype
65	reduces nuclear localization activity of znf268; when associated with a-68.
68	reduces nuclear localization activity of znf268; when associated with a-65.
306	disrupts the interaction with znf350 and amost completely relieves the transcription repressive effect of sumoylated tri
366	greatly reduced interaction with ppp1ca.
368	increased interaction with ppp1ca. greatly decreased phosphorylation on s-824.
370	some reduction in interaction with ppp1ca.
440	no effect on interaction with ppp1ca nor on sumoylation levels. decreased sumoylation levels; when associated with d-501
488	abolishes interaction with cbx5; when associated with e-490.
490	abolishes interaction with cbx5; when associated with e-488.
501	no effect on interaction with ppp1ca nor on sumoylation levels. decreased sumoylation levels; when associated with d-440
554	moderately reduces sumoylation and repression. abolishes both sumoylation and repression; when associated with r-575. re
575	modestly reduced sumoylation and repression. abolishes both sumoylation and repression; when associated with r-554.
651	complete loss of the phd finger-mediated stimulatory effect on sumoylation. loss of binding ube2i.
653	greatly reduced sumoylation. little further effect on sumoylation; when associated with a-668 and/or a-709.
668	little effect on sumoylation. little further effect on sumoylation; when associated with a-653 and/or a-709.
676	modestly reduces sumoylation and repression.
709	greatly reduced sumoylation. little further effect on sumoylation; when associated with a-653 and/or a-668.
750	some reduced sumoylation and repression.
779	abolishes both sumoylation and repression; when associated with r-804. relieves the repressor activity on dox-induced ga
804	abolishes both sumoylation and repression; when associated with r-779. relieves the repressor activity on dox-induced ga
824	suppresses dox-induced cdkn1a/p21 promoter activation. no effect on sumoylation levels. decreased sumoylation levels; wh
824	enhances dox-induced cdkn1a/p21 promoter activation. decreased sumoylation with or without dox-treatment.

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-9609690	HCMV Early Events
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-1643685	Disease
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9609646	HCMV Infection
R-HSA-9824446	Viral Infection Pathways
R-HSA-9842860	Regulation of endogenous retroelements

MSigDB gene sets: 406 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, MORF_ESPL1, MORF_SMC1L1, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCM_NPM1, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, MORF_UBE2I, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_GROWTH, MORF_HDAC1

GO Biological Process (22): negative regulation of transcription by RNA polymerase II (GO:0000122), epithelial to mesenchymal transition (GO:0001837), DNA repair (GO:0006281), chromatin organization (GO:0006325), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), embryo implantation (GO:0007566), protein sumoylation (GO:0016925), positive regulation of protein import into nucleus (GO:0042307), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), suppression of viral release by host (GO:0044790), innate immune response (GO:0045087), positive regulation of DNA repair (GO:0045739), negative regulation of single stranded viral RNA replication via double stranded DNA intermediate (GO:0045869), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), convergent extension involved in axis elongation (GO:0060028), embryonic placenta morphogenesis (GO:0060669), genomic imprinting (GO:0071514), in utero embryonic development (GO:0001701), positive regulation of macromolecule metabolic process (GO:0010604), epigenetic programming of gene expression (GO:0043045), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935)

GO Molecular Function (19): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), protein kinase activity (GO:0004672), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), SUMO transferase activity (GO:0019789), ubiquitin protein ligase binding (GO:0031625), Krueppel-associated box domain binding (GO:0035851), ubiquitin protein ligase activity (GO:0061630), chromo shadow domain binding (GO:0070087), promoter-specific chromatin binding (GO:1990841), transcription coregulator activity (GO:0003712), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872), ubiquitin-like protein ligase activity (GO:0061659)

GO Cellular Component (7): euchromatin (GO:0000791), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), protein-containing complex (GO:0032991), RNA polymerase II transcription regulator complex (GO:0090575), chromatin (GO:0000785)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Gene expression (Transcription)	2
RNA Polymerase II Transcription	1
SUMO E3 ligases SUMOylate target proteins	1
HCMV Infection	1
Regulation of endogenous retroelements	1
Post-translational protein modification	1
SUMOylation	1
Disease	1
Metabolism of proteins	1
Viral Infection Pathways	1
Infectious disease	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ubiquitin-like protein transferase activity	3
negative regulation of DNA-templated transcription	2
negative regulation of RNA biosynthetic process	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
nucleic acid binding	2
binding	2
transcription coregulator activity	2
protein domain specific binding	2
chromatin	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
mesenchymal cell differentiation	1
DNA metabolic process	1
DNA damage response	1
cellular component organization	1
constitutive heterochromatin formation	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
defense response to virus	1
immune response	1
defense response to symbiont	1
DNA repair	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
single stranded viral RNA replication via double stranded DNA intermediate	1
negative regulation of viral genome replication	1
regulation of single stranded viral RNA replication via double stranded DNA intermediate	1

Protein interactions and networks

STRING

5238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM28	SETDB1	Q15047	996
TRIM28	MAGEA3	P43357	987
TRIM28	K7ESF6	K7ESF6	981
TRIM28	ZNF44	P15621	981
TRIM28	ZNF569	Q5MCW4	981
TRIM28	ZNF501	Q96CX3	981
TRIM28	ZNF436	Q9C0F3	981
TRIM28	ZFP57	Q9NU63	981
TRIM28	ZNF629	Q9UEG4	981
TRIM28	CBX5	P45973	973
TRIM28	DNMT1	P26358	957
TRIM28	MAGEC2	Q9UBF1	957
TRIM28	ZKSCAN7	Q9P0L1	944
TRIM28	CHD3	Q12873	934
TRIM28	ZNF10	P21506	930

IntAct

525 interactions, top by confidence:

A	B	Type	Score
TRIM28	CBX5	psi-mi:“MI:0915”(physical association)	0.910
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
TRIM33	TRIM24	psi-mi:“MI:0914”(association)	0.790
RRP1B	NPM1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
TRIM28	TRIM24	psi-mi:“MI:0914”(association)	0.600
TRIM28	CHD3	psi-mi:“MI:0915”(physical association)	0.570
TRIM28	NCOR1	psi-mi:“MI:0915”(physical association)	0.560
NCOR1	TRIM28	psi-mi:“MI:0915”(physical association)	0.560
TRIM28	NCOR1	psi-mi:“MI:0403”(colocalization)	0.560
Haus4	HAUS5	psi-mi:“MI:0915”(physical association)	0.560
ZNF10	TRIM28	psi-mi:“MI:0915”(physical association)	0.550
TRIM28		psi-mi:“MI:0407”(direct interaction)	0.540
TRIM28		psi-mi:“MI:0915”(physical association)	0.540
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530

BioGRID (2404): TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-Western), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM28 (Biochemical Activity), TRIM28 (Reconstituted Complex)

ESM2 similar proteins: A0JNG4, A1L3T7, B1AVH7, B5DFA1, D2H0G5, E1U8D0, E9QHE3, I1VZH0, O08629, O60826, O75052, O94964, P58660, P86182, P98171, Q13263, Q149G0, Q1LWB0, Q1RMI8, Q3ULW6, Q3V3A7, Q571B6, Q58D79, Q5JV73, Q5R8S0, Q62318, Q6P4K6, Q6PGG2, Q6ZQ29, Q6ZRF8, Q768S4, Q7TSI1, Q80TQ5, Q8BL43, Q8C7B8, Q8IWE5, Q8K1S6, Q8N163, Q8TF30, Q8VDP4

Diamond homologs: D3ZHA0, D3ZVM4, E1BJS7, E7FAM5, F6QEU4, M9PH32, O08629, O75369, P13466, Q13263, Q14315, Q1PRL4, Q1PSW8, Q2Q1W2, Q62318, Q80X90, Q8VHX6, Q9VEN1, A2A8L1, A2BIL7, A6H619, A7E320, A8DZJ1, D3ZD32, O15164, O97159, Q09477, Q12830, Q12873, Q14839, Q63625, Q64127, Q6E2N3, Q6PDQ2, Q6ZPK0, Q8TDI0, Q96BD5, Q9UIG0, Q9W0T1, Q9Z277

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
PRKCD	down-regulates	TRIM28	phosphorylation
SMARCAD1	“up-regulates activity”	TRIM28	binding
TRIM28	“up-regulates activity”	MDM2	binding
TRIM28	“down-regulates quantity by repression”	ALDOA	“transcriptional regulation”
TRIM28	“down-regulates quantity by destabilization”	FBP1	ubiquitination
MAGEA3	“up-regulates activity”	TRIM28	binding
MAGEC2	“up-regulates activity”	TRIM28	binding
TRIM28	“down-regulates quantity by repression”	Aldolase	“transcriptional regulation”
PPP1CA	“up-regulates activity”	TRIM28	dephosphorylation
PPP4C	“down-regulates activity”	TRIM28	dephosphorylation
RIPK3	“down-regulates activity”	TRIM28	phosphorylation
CHEK2	“down-regulates activity”	TRIM28	phosphorylation
SRC	“down-regulates activity”	TRIM28	phosphorylation
CHEK1	“up-regulates activity”	TRIM28	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 206 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
DNA Double-Strand Break Repair	6	10.5×	2e-03
Oncogenic MAPK signaling	6	10.5×	2e-03
Selective autophagy	5	9.8×	9e-03
Antimicrobial mechanism of IFN-stimulated genes	6	8.3×	6e-03
Interferon Signaling	9	7.6×	1e-03
SUMO E3 ligases SUMOylate target proteins	6	7.5×	9e-03
Signaling by BRAF and RAF1 fusions	6	7.2×	1e-02
Interferon gamma signaling	8	7.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
macrophage differentiation	5	13.1×	6e-03
heterochromatin formation	7	10.0×	3e-03
cellular response to virus	8	9.0×	2e-03
positive regulation of translation	7	8.9×	4e-03
G1/S transition of mitotic cell cycle	7	7.8×	6e-03
negative regulation of translation	7	7.7×	6e-03
DNA damage response	17	5.1×	4e-05
chromatin remodeling	11	4.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	2
Uncertain significance	137
Likely benign	113
Benign	25

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1691525	NM_005762.3(TRIM28):c.991C>T (p.Gln331Ter)	Pathogenic
3377811	NM_005762.3(TRIM28):c.477dup (p.Ala160fs)	Pathogenic
3725638	NM_005762.3(TRIM28):c.1931_1932del (p.Glu644fs)	Pathogenic
4082139	NM_005762.3(TRIM28):c.525_526del (p.Glu175fs)	Pathogenic
4082140	NM_005762.3(TRIM28):c.1746_1747delinsC (p.Glu583fs)	Pathogenic
4082141	NM_005762.3(TRIM28):c.1015C>T (p.Gln339Ter)	Pathogenic
4082142	G310D	Pathogenic
4717378	NM_005762.3(TRIM28):c.1026_1027dup (p.Glu343fs)	Pathogenic
4736187	NM_005762.3(TRIM28):c.1841del (p.Pro614fs)	Pathogenic
973190	NM_005762.3(TRIM28):c.2101C>T (p.Gln701Ter)	Pathogenic
3655749	NM_005762.3(TRIM28):c.839+1G>A	Likely pathogenic
4056100	NM_005762.3(TRIM28):c.1216+1G>T	Likely pathogenic

SpliceAI

2162 predictions. Top by Δscore:

Variant	Effect	Δscore
19:58545095:CCGGT:C	donor_loss	1.0000
19:58545096:CGGTA:C	donor_loss	1.0000
19:58545098:G:GG	donor_gain	1.0000
19:58545098:GTAA:G	donor_loss	1.0000
19:58545099:T:A	donor_loss	1.0000
19:58545413:T:TA	acceptor_gain	1.0000
19:58545420:C:CA	acceptor_gain	1.0000
19:58545423:A:AG	acceptor_gain	1.0000
19:58545424:G:GG	acceptor_gain	1.0000
19:58545536:AGGT:A	donor_loss	1.0000
19:58545538:G:T	donor_loss	1.0000
19:58545539:T:G	donor_loss	1.0000
19:58545762:A:AG	acceptor_gain	1.0000
19:58545763:G:GG	acceptor_gain	1.0000
19:58545763:GT:G	acceptor_gain	1.0000
19:58545763:GTGCT:G	acceptor_gain	1.0000
19:58545862:G:GT	donor_gain	1.0000
19:58545875:G:GT	donor_gain	1.0000
19:58545906:GC:G	donor_gain	1.0000
19:58547509:CCA:C	donor_gain	1.0000
19:58547510:CA:C	donor_gain	1.0000
19:58547512:G:GG	donor_gain	1.0000
19:58547588:T:TA	acceptor_gain	1.0000
19:58547592:CTCA:C	acceptor_loss	1.0000
19:58547595:A:AG	acceptor_gain	1.0000
19:58547595:AG:A	acceptor_gain	1.0000
19:58547596:G:A	acceptor_loss	1.0000
19:58547596:G:GC	acceptor_gain	1.0000
19:58547596:GG:G	acceptor_gain	1.0000
19:58547596:GGT:G	acceptor_gain	1.0000

AlphaMissense

5416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:58544951:G:A	C65Y	1.000
19:58545004:T:C	C83R	1.000
19:58545433:T:A	C117S	1.000
19:58545433:T:C	C117R	1.000
19:58545434:G:A	C117Y	1.000
19:58545434:G:C	C117S	1.000
19:58545435:T:G	C117W	1.000
19:58545442:T:A	C120S	1.000
19:58545442:T:C	C120R	1.000
19:58545443:G:A	C120Y	1.000
19:58545443:G:C	C120S	1.000
19:58545480:T:A	N132K	1.000
19:58545480:T:G	N132K	1.000
19:58545484:T:C	F134L	1.000
19:58545485:T:C	F134S	1.000
19:58545485:T:G	F134C	1.000
19:58545486:C:A	F134L	1.000
19:58545486:C:G	F134L	1.000
19:58545767:T:A	C153S	1.000
19:58545767:T:C	C153R	1.000
19:58545768:G:A	C153Y	1.000
19:58545768:G:C	C153S	1.000
19:58545768:G:T	C153F	1.000
19:58545769:C:G	C153W	1.000
19:58545773:A:C	S155R	1.000
19:58545775:C:A	S155R	1.000
19:58545775:C:G	S155R	1.000
19:58545776:T:A	C156S	1.000
19:58545776:T:C	C156R	1.000
19:58545777:G:A	C156Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000017709 (19:58544053 C>T), RS1000381582 (19:58546755 G>A), RS1000432480 (19:58546620 C>G), RS1000618511 (19:58543087 T>C,G), RS1000718216 (19:58547819 G>A), RS1000767261 (19:58547567 G>C), RS1002315257 (19:58544736 G>T), RS1002450731 (19:58544890 T>A,C,G), RS1002668806 (19:58550185 T>C), RS1002979683 (19:58543292 G>A,C), RS1003113624 (19:58543596 G>T), RS1003200880 (19:58547443 G>C,T), RS1003312008 (19:58544309 G>A), RS1003447518 (19:58544412 G>A,T), RS1003795670 (19:58544262 C>T)

Disease associations

OMIM: gene MIM:601742 | disease phenotypes: MIM:194070, MIM:621332

GenCC curated gene-disease

Disease	Classification	Inheritance
childhood kidney Wilms tumor	Definitive	Autosomal dominant
kidney Wilms tumor	Supportive	Autosomal dominant

Mondo (7): Wilms tumor 1 (MONDO:0008679), prostate cancer (MONDO:0008315), Wilms tumor 7 (MONDO:0979876), familial colorectal cancer (MONDO:0023113), Wilms tumor (MONDO:0006058), kidney Wilms tumor (MONDO:0019004), childhood kidney Wilms tumor (MONDO:0024676)

Orphanet (2): Nephroblastoma (Orphanet:654), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000086	Ectopic kidney
HP:0000526	Aniridia
HP:0000822	Hypertension
HP:0001528	Hemihypertrophy
HP:0001824	Weight loss
HP:0001901	Polycythemia
HP:0001903	Anemia
HP:0001945	Fever
HP:0002027	Abdominal pain
HP:0002094	Dyspnea
HP:0002664	Neoplasm
HP:0002667	Nephroblastoma
HP:0002716	Lymphadenopathy
HP:0002896	Neoplasm of the liver
HP:0002907	Microscopic hematuria
HP:0003072	Hypercalcemia
HP:0003593	Infantile onset
HP:0005580	Duplication of renal pelvis
HP:0008330	Reduced von Willebrand factor activity
HP:0011463	Childhood onset
HP:0012587	Macroscopic hematuria
HP:0012871	Varicocele
HP:0031105	Abnormal uterus morphology
HP:0031500	Abdominal mass
HP:0033834	Malaise
HP:0100526	Neoplasm of the lung

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002390_664	Mean corpuscular hemoglobin	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D009396	Wilms Tumor	C04.557.435.595; C04.588.945.947.535.585; C04.700.900; C12.050.351.937.820.535.585; C12.050.351.968.419.473.585; C12.200.758.820.750.585; C12.200.777.419.473.585; C12.900.820.535.585; C12.950.419.473.585; C12.950.983.535.585; C16.320.700.900

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3769297 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — TIF1 family

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.10	Kd	78.69	nM	CHEMBL5653589
7.10	ED50	78.69	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 25 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149656: Binding affinity to human TRIM28 incubated for 45 mins by Kinobead based pull down assay	kd	0.0787	uM

CTD chemical–gene interactions

67 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases abundance, increases expression	2
2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one	decreases reaction, increases phosphorylation, increases expression, increases reaction	2
Ascorbic Acid	decreases reaction, increases expression	2
Caffeine	affects phosphorylation, decreases expression	2
Hydrogen Peroxide	decreases reaction, increases phosphorylation, increases reaction, increases expression	2
Valproic Acid	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
bufotalin	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
deoxynivalenol	increases expression	1
lead acetate	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
potassium chromate(VI)	decreases reaction, increases expression, increases reaction	1
coumarin	affects phosphorylation	1
nivalenol	increases expression	1
epigallocatechin gallate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
ICG 001	decreases expression	1
abrine	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	increases expression	1
bisphenol S	increases expression	1
2-(2,6-dimethylmorpholin-4-yl)-N-(5-(6-morpholin-4-yl-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl)acetamide	decreases reaction, increases expression	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3773286	Binding	Binding affinity to biotinylated TRIM28 (unknown origin) expressed in Escherichia coli at 0.2 to 1 uM by Biolayer Interferometric analysis	Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B. — J Med Chem

Cellosaurus cell lines

10 cell lines: 6 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7Q0	SEES3-1V human TRIM28, clone1	Embryonic stem cell	Male
CVCL_A7Q1	SEES3-1V human TRIM28, clone2	Embryonic stem cell	Male
CVCL_A7Q2	SEES3-1V human TRIM28, clone3	Embryonic stem cell	Male
CVCL_B8RD	Abcam HCT 116 TRIM28 KO	Cancer cell line	Male
CVCL_B9TS	Abcam A-549 TRIM28 KO	Cancer cell line	Male
CVCL_D8D4	Ubigene A-549 TRIM28 KO	Cancer cell line	Male
CVCL_D8XS	Ubigene HCT 116 TRIM28 KO	Cancer cell line	Male
CVCL_RX69	HEK293 pcDNA5/FRT/TO-KAP1	Transformed cell line	Female
CVCL_TU02	HAP1 TRIM28 (-) 1	Cancer cell line	Male
CVCL_TU03	HAP1 TRIM28 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00336531	PHASE4	COMPLETED	Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer