Human Gene TRIM24 (uc003vuc.3)
  Description: Homo sapiens tripartite motif containing 24 (TRIM24), transcript variant 1, mRNA.
RefSeq Summary (NM_015905): The protein encoded by this gene mediates transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors, including the estrogen, retinoic acid, and vitamin D3 receptors. The protein localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. The protein is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains - a RING, a B-box type 1 and a B-box type 2 - and a coiled-coil region. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr7:138,145,079-138,270,332 Size: 125,254 Total Exon Count: 19 Strand: +
Coding Region
   Position: hg19 chr7:138,145,294-138,269,696 Size: 124,403 Coding Exon Count: 19 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:138,145,079-138,270,332)mRNA (may differ from genome)Protein (1050 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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GeneCardsGeneNetworkH-INVHGNCHPRDLynx
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: TIF1A_HUMAN
DESCRIPTION: RecName: Full=Transcription intermediary factor 1-alpha; Short=TIF1-alpha; EC=6.3.2.-; AltName: Full=E3 ubiquitin-protein ligase TRIM24; AltName: Full=RING finger protein 82; AltName: Full=Tripartite motif-containing protein 24;
FUNCTION: Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity).
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Interacts with CARM1, NCOA2/GRIP1, PML, KAT5/TIP60, BRD7, CBX1, CBX3 and CBX5. Part of a coactivator complex containing TRIM24, NCOA2 and CARM1 (By similarity). Interacts with NR3C2/MCR. Interacts with the ligand-binding domain of estrogen receptors (in vitro). Interaction with DNA-bound estrogen receptors requires the presence of estradiol. Interacts with AR and p53/TP53. Interacts (via bromo domain) with histone H3 (via N-terminus), provided that it is not methylated at 'Lys-4' (H3K4me0). Does not interact with histone H3 that is methylated at 'Lys-4' (H3K4me1, H3K4me2 or H3K4me3). Interacts (via bromo domain) with histone H3 (via N- terminus) that is acetylated at 'Lys-23' (H3K23ac). Has the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has very low affinity for histone H3 that is methylated at 'Lys-9' (H3K9me), or acetylated at both 'Lys-9' (H3K9ac) and 'Lys-14' (H3K14ac), or acetylated at 'Lys-27' (H3K27ac) (in vitro).
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Colocalizes with sites of active transcription. Detected both in nucleus and cytoplasm in some breast cancer samples. Predominantly nuclear.
INDUCTION: Up-regulated in some cases of breast cancer.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
PTM: Sumoylated (By similarity).
DISEASE: Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:188550]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM24/TIF1 is found in thyroid papillary carcinomas. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene.
SIMILARITY: Contains 2 B box-type zinc fingers.
SIMILARITY: Contains 1 bromo domain.
SIMILARITY: Contains 1 PHD-type zinc finger.
SIMILARITY: Contains 1 RING-type zinc finger.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TRIM24ID504ch7q34.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TRIM24
CDC HuGE Published Literature: TRIM24
Positive Disease Associations: Body Weight , quantitative traits
Related Studies:
  1. Body Weight
    Jennifer K Lowe et al. PLoS genetics 2009, Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae., PLoS genetics. [PubMed 19197348]
  2. quantitative traits
    Lowe ,et al. 2009, Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae, PLoS genetics 2009 5- 2 : e1000365. [PubMed 19197348]

-  MalaCards Disease Associations
  MalaCards Gene Search: TRIM24
Diseases sorted by gene-association score: differentiated thyroid carcinoma* (117), cerebellar agenesis (4), 8p11 myeloproliferative syndrome (2), breast cancer (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 10.80 RPKM in Adrenal Gland
Total median expression: 147.11 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -108.20215-0.503 Picture PostScript Text
3' UTR -153.67636-0.242 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003649 - Bbox_C
IPR001487 - Bromodomain
IPR018359 - Bromodomain_CS
IPR019786 - Zinc_finger_PHD-type_CS
IPR000315 - Znf_B-box
IPR011011 - Znf_FYVE_PHD
IPR001965 - Znf_PHD
IPR019787 - Znf_PHD-finger
IPR001841 - Znf_RING
IPR013083 - Znf_RING/FYVE/PHD
IPR017907 - Znf_RING_CS

Pfam Domains:
PF00439 - Bromodomain
PF00628 - PHD-finger
PF00643 - B-box zinc finger
PF13445 - RING-type zinc-finger

SCOP Domains:
47370 - Bromodomain
57845 - B-box zinc-binding domain
57850 - RING/U-box
57903 - FYVE/PHD zinc finger

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2YYN - X-ray MuPIT 3O33 - X-ray MuPIT 3O34 - X-ray MuPIT 3O35 - X-ray MuPIT 3O36 - X-ray MuPIT 3O37 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O15164
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
 Gene Details    
 Gene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0002039 p53 binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003713 transcription coactivator activity
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004842 ubiquitin-protein transferase activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016740 transferase activity
GO:0016922 ligand-dependent nuclear receptor binding
GO:0034056 estrogen response element binding
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding
GO:0061630 ubiquitin protein ligase activity
GO:0070577 lysine-acetylated histone binding
GO:0035064 methylated histone binding

Biological Process:
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0006468 protein phosphorylation
GO:0008285 negative regulation of cell proliferation
GO:0010628 positive regulation of gene expression
GO:0016567 protein ubiquitination
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0030163 protein catabolic process
GO:0031647 regulation of protein stability
GO:0042981 regulation of apoptotic process
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0046777 protein autophosphorylation
GO:0055074 calcium ion homeostasis
GO:0070562 regulation of vitamin D receptor signaling pathway
GO:0071391 cellular response to estrogen stimulus
GO:1901796 regulation of signal transduction by p53 class mediator

Cellular Component:
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005719 nuclear euchromatin
GO:0005726 perichromatin fibrils
GO:0005737 cytoplasm
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  AK312610 - Homo sapiens cDNA, FLJ92991.
AK075306 - Homo sapiens cDNA FLJ90825 fis, clone Y79AA1001523, highly similar to Transcription intermediary factor 1-alpha.
LF384092 - JP 2014500723-A/191595: Polycomb-Associated Non-Coding RNAs.
AK302679 - Homo sapiens cDNA FLJ53462 complete cds, highly similar to Transcription intermediary factor 1-alpha.
AF119042 - Homo sapiens transcriptional intermediary factor 1 alpha mRNA, complete cds.
BC028689 - Homo sapiens tripartite motif-containing 24, mRNA (cDNA clone MGC:26421 IMAGE:4827559), complete cds.
AB528587 - Synthetic construct DNA, clone: pF1KB4125, Homo sapiens TRIM24 gene for tripartite motif-containing protein 24, without stop codon, in Flexi system.
AF009353 - Homo sapiens transcription intermediary factor 1 (TIF1) mRNA, complete cds.
AK127592 - Homo sapiens cDNA FLJ45687 fis, clone FCBBF3020030, highly similar to Transcription intermediary factor 1-alpha.
MA619669 - JP 2018138019-A/191595: Polycomb-Associated Non-Coding RNAs.
LF361715 - JP 2014500723-A/169218: Polycomb-Associated Non-Coding RNAs.
JD460913 - Sequence 441937 from Patent EP1572962.
JD187217 - Sequence 168241 from Patent EP1572962.
JD069241 - Sequence 50265 from Patent EP1572962.
JD458250 - Sequence 439274 from Patent EP1572962.
JD469824 - Sequence 450848 from Patent EP1572962.
MA597292 - JP 2018138019-A/169218: Polycomb-Associated Non-Coding RNAs.
LF361719 - JP 2014500723-A/169222: Polycomb-Associated Non-Coding RNAs.
LF361720 - JP 2014500723-A/169223: Polycomb-Associated Non-Coding RNAs.
LF361722 - JP 2014500723-A/169225: Polycomb-Associated Non-Coding RNAs.
LF361727 - JP 2014500723-A/169230: Polycomb-Associated Non-Coding RNAs.
AL360186 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 446686.
LF361728 - JP 2014500723-A/169231: Polycomb-Associated Non-Coding RNAs.
LF361730 - JP 2014500723-A/169233: Polycomb-Associated Non-Coding RNAs.
LF361731 - JP 2014500723-A/169234: Polycomb-Associated Non-Coding RNAs.
LF361733 - JP 2014500723-A/169236: Polycomb-Associated Non-Coding RNAs.
LF361735 - JP 2014500723-A/169238: Polycomb-Associated Non-Coding RNAs.
JD374791 - Sequence 355815 from Patent EP1572962.
JD335599 - Sequence 316623 from Patent EP1572962.
LF361736 - JP 2014500723-A/169239: Polycomb-Associated Non-Coding RNAs.
JD434674 - Sequence 415698 from Patent EP1572962.
JD335057 - Sequence 316081 from Patent EP1572962.
LF361737 - JP 2014500723-A/169240: Polycomb-Associated Non-Coding RNAs.
LF361738 - JP 2014500723-A/169241: Polycomb-Associated Non-Coding RNAs.
JD096732 - Sequence 77756 from Patent EP1572962.
LF361739 - JP 2014500723-A/169242: Polycomb-Associated Non-Coding RNAs.
MA597296 - JP 2018138019-A/169222: Polycomb-Associated Non-Coding RNAs.
MA597297 - JP 2018138019-A/169223: Polycomb-Associated Non-Coding RNAs.
MA597299 - JP 2018138019-A/169225: Polycomb-Associated Non-Coding RNAs.
MA597304 - JP 2018138019-A/169230: Polycomb-Associated Non-Coding RNAs.
MA597305 - JP 2018138019-A/169231: Polycomb-Associated Non-Coding RNAs.
MA597307 - JP 2018138019-A/169233: Polycomb-Associated Non-Coding RNAs.
MA597308 - JP 2018138019-A/169234: Polycomb-Associated Non-Coding RNAs.
MA597310 - JP 2018138019-A/169236: Polycomb-Associated Non-Coding RNAs.
MA597312 - JP 2018138019-A/169238: Polycomb-Associated Non-Coding RNAs.
MA597313 - JP 2018138019-A/169239: Polycomb-Associated Non-Coding RNAs.
MA597314 - JP 2018138019-A/169240: Polycomb-Associated Non-Coding RNAs.
MA597315 - JP 2018138019-A/169241: Polycomb-Associated Non-Coding RNAs.
MA597316 - JP 2018138019-A/169242: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O15164 (Reactome details) participates in the following event(s):

R-HSA-1839031 Dimerization of cytosolic FGFR1 fusion proteins
R-HSA-1839039 Tyrosine kinase inhibitors bind and inhibit cytosolic FGFR1 fusion dimer phosphorylation
R-HSA-1839065 Phosphorylation of cytosolic FGFR1 fusion dimers
R-HSA-6802927 BRAF and RAF fusion mutant dimers are phosphorylated
R-HSA-6802934 p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs
R-HSA-6802932 Dissociation of BRAF/RAF fusion complex
R-HSA-1839080 Activated cytosolic FGFR1 fusions bind PIK3CA
R-HSA-6802933 p-BRAF and RAF fusion dimers phosphorylate MAP2Ks
R-HSA-6802935 MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers
R-HSA-1839094 Activated FGFR1 mutants and fusions bind PLCG1
R-HSA-1839100 p-4Y- PLCG1 dissociates from activated FGFR1 mutants and fusions
R-HSA-1839091 Cytosolic FGFR1 fusion protein-associated PI3K phosphorylates PIP2 to PIP3
R-HSA-1839098 Activated FGFR1 mutants and fusions phosphorylate PLCG1
R-HSA-1839117 Signaling by cytosolic FGFR1 fusion mutants
R-HSA-1839124 FGFR1 mutant receptor activation
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-6802957 Oncogenic MAPK signaling
R-HSA-1226099 Signaling by FGFR in disease
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: A4D1R7, A4D1R8, NM_015905, NP_056989, O15164, O95854, RNF82, TIF1, TIF1A, TIF1A_HUMAN
UCSC ID: uc003vuc.3
RefSeq Accession: NM_015905
Protein: O15164 (aka TIF1A_HUMAN)
CCDS: CCDS5847.1, CCDS47720.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_015905.2
exon count: 19CDS single in 3' UTR: no RNA size: 4007
ORF size: 3153CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6506.00frame shift in genome: no % Coverage: 99.93
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.