Human Gene TRIM33 (ENST00000358465.7) from GENCODE V44
  Description: Homo sapiens tripartite motif containing 33 (TRIM33), transcript variant a, mRNA. (from RefSeq NM_015906)
RefSeq Summary (NM_015906): The protein encoded by this gene is thought to be a transcriptional corepressor. However, molecules that interact with this protein have not yet been identified. The protein is a member of the tripartite motif family. This motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. Three alternatively spliced transcript variants for this gene have been described, however, the full-length nature of one variant has not been determined. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000358465.7
Gencode Gene: ENSG00000197323.12
Transcript (Including UTRs)
   Position: hg38 chr1:114,392,790-114,511,203 Size: 118,414 Total Exon Count: 20 Strand: -
Coding Region
   Position: hg38 chr1:114,397,648-114,511,076 Size: 113,429 Coding Exon Count: 20 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:114,392,790-114,511,203)mRNA (may differ from genome)Protein (1127 aa)
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GeneCardsHGNCHPRDLynxMalacardsMGI
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TRI33_HUMAN
DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase TRIM33; EC=6.3.2.-; AltName: Full=Ectodermin homolog; AltName: Full=RET-fused gene 7 protein; Short=Protein Rfg7; AltName: Full=Transcription intermediary factor 1-gamma; Short=TIF1-gamma; AltName: Full=Tripartite motif-containing protein 33;
FUNCTION: Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed:16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF- beta/BMP signaling cascade).
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Homooligomer and heterooligomer with TRIM24 and TRIM28 family members. Interacts with SMAD4 in unstimulated cells. Found in a complex with SMAD2 and SMAD3 upon addition of TGF-beta. Interacts with SMAD2 and SMAD3. Interacts with SMAD4 under basal and induced conditions and, upon TGF-beta signaling, with activated SMAD2. Forms a ternary complex with SMAD4 and SMAD2 upon TGF-beta signaling.
INTERACTION: Q15796:SMAD2; NbExp=6; IntAct=EBI-2214398, EBI-1040141; Q13485:SMAD4; NbExp=5; IntAct=EBI-2214398, EBI-347263;
SUBCELLULAR LOCATION: Nucleus. Note=In discrete nuclear dots resembling nuclear bodies (By similarity).
TISSUE SPECIFICITY: Expressed in stem cells at the bottom of the crypts of the colon (at protein level). Expressed in colon adenomas and adenocarcinomas (at protein level). Expressed in brain, lung, liver, spleen, thymus, prostate, kidney, testis, heart, placenta, pancreas, small intestine, ovary, colon, skeletal muscle and hematopoietic progenitors.
DISEASE: Defects in TRIM33 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 TRIM33 is found in thyroid papillary carcinomas. Translocation t(1;10)(p13;q11) with RET. The translocation generates the TRIM33/RET (PTC7) oncogene.
SIMILARITY: Belongs to the TRIM/RBCC family.
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.
SEQUENCE CAUTION: Sequence=AAD17259.1; Type=Frameshift; Positions=1114; Sequence=BAA83065.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAI13548.1; Type=Erroneous gene model prediction; Sequence=CAI21895.1; Type=Erroneous gene model prediction;

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: TRIM33
Diseases sorted by gene-association score: differentiated thyroid carcinoma* (71), myositis (3), endocervicitis (2), trench fever (2), hymenolepiasis (1), enterobiasis (1), norwegian scabies (1), suppurative cholangitis (1)
* = Manually curated disease association

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

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 11.73 RPKM in Testis
Total median expression: 318.80 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 -67.50127-0.531 Picture PostScript Text
3' UTR -1053.644858-0.217 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
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
PF13639 - Ring finger domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3U5M - X-ray MuPIT 3U5N - X-ray MuPIT 3U5O - X-ray MuPIT 3U5P - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9UPN9
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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
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016740 transferase activity
GO:0046872 metal ion binding
GO:0070410 co-SMAD binding
GO:0070412 R-SMAD binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0016567 protein ubiquitination
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0030514 negative regulation of BMP signaling pathway
GO:0045892 negative regulation of transcription, DNA-templated

Cellular Component:
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm


-  Descriptions from all associated GenBank mRNAs
  AK301997 - Homo sapiens cDNA FLJ55940 complete cds, highly similar to Transcription intermediary factor 1-gamma.
AK023434 - Homo sapiens cDNA FLJ13372 fis, clone PLACE1000706, highly similar to Transcription intermediary factor 1-gamma.
AF119043 - Homo sapiens transcriptional intermediary factor 1 gamma mRNA, complete cds.
AF220136 - Homo sapiens tripartite motif protein TRIM33 alpha (TRIM33) mRNA, complete cds; alternatively spliced.
AF220137 - Homo sapiens tripartite motif protein TRIM33 beta mRNA, complete cds; alternatively spliced.
AB029036 - Homo sapiens KIAA1113 mRNA for KIAA1113 protein.
AK057487 - Homo sapiens cDNA FLJ32925 fis, clone TESTI2007183, highly similar to Homo sapiens transcriptional intermediary factor 1 gamma mRNA.
AJ132948 - Homo sapiens mRNA for rfg7 protein, partial.
AB384564 - Synthetic construct DNA, clone: pF1KA1113, Homo sapiens TRIM33 gene for tripartite motif-containing protein 33, complete cds, without stop codon, in Flexi system.
AL080216 - Homo sapiens mRNA; cDNA DKFZp586K1123 (from clone DKFZp586K1123).
AK021491 - Homo sapiens cDNA FLJ11429 fis, clone HEMBA1001077, weakly similar to Homo sapiens transcriptional intermediary factor 1 gamma mRNA.
AB075517 - Homo sapiens neuroblastoma cDNA, clone:Nbla00540, full insert sequence.

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

Protein Q9UPN9 (Reactome details) participates in the following event(s):

R-HSA-870538 TRIM33 (Ectodermin) binds SMAD heterotrimer in the nucleus
R-HSA-870449 TRIM33 monoubiquitinates SMAD4
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-170834 Signaling by TGF-beta Receptor Complex
R-HSA-212436 Generic Transcription Pathway
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-162582 Signal Transduction
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000358465.1, ENST00000358465.2, ENST00000358465.3, ENST00000358465.4, ENST00000358465.5, ENST00000358465.6, KIAA1113, NM_015906, O95855, Q5TG72, Q5TG73, Q5TG74, Q9C017, Q9UJ79, Q9UPN9, RFG7, TIF1G, TRI33_HUMAN, uc001eew.1, uc001eew.2, uc001eew.3, uc001eew.4
UCSC ID: ENST00000358465.7
RefSeq Accession: NM_015906
Protein: Q9UPN9 (aka TRI33_HUMAN)
CCDS: CCDS872.1, CCDS873.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.