Human Gene TRIM25 (ENST00000316881.9) Description and Page Index
  Description: Homo sapiens tripartite motif containing 25 (TRIM25), mRNA. (from RefSeq NM_005082)
RefSeq Summary (NM_005082): The protein encoded by this gene 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. The protein localizes to the cytoplasm. The presence of potential DNA-binding and dimerization-transactivation domains suggests that this protein may act as a transcription factor, similar to several other members of the TRIM family. Expression of the gene is upregulated in response to estrogen, and it is thought to mediate estrogen actions in breast cancer as a primary response gene. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000316881.9
Gencode Gene: ENSG00000121060.18
Transcript (Including UTRs)
   Position: hg38 chr17:56,887,909-56,914,049 Size: 26,141 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg38 chr17:56,891,700-56,913,988 Size: 22,289 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2019-09-04

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr17:56,887,909-56,914,049)mRNA (may differ from genome)Protein (630 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=E3 ubiquitin/ISG15 ligase TRIM25; EC=; EC=6.3.2.n3; AltName: Full=Estrogen-responsive finger protein; AltName: Full=RING finger protein 147; AltName: Full=Tripartite motif-containing protein 25; AltName: Full=Ubiquitin/ISG15-conjugating enzyme TRIM25; AltName: Full=Zinc finger protein 147;
FUNCTION: Functions as an ubiquitin E3 ligase and as an ISG15 E3 ligase. Involved in innate immune defense against viruses by mediating ubiquitination of DDX58. Mediates 'Lys-63'-linked polyubiquitination of the DDX58 N-terminal CARD-like region which is crucial for triggering the cytosolic signal transduction that leads to the production of interferons in response to viral infection. Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway. Mediates estrogen action in various target organs.
CATALYTIC ACTIVITY: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
CATALYTIC ACTIVITY: ATP + [ISG15] + [protein]-lysine = AMP + diphosphate + [protein]-N-ISGyllysine.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Interacts (via SPRY domain) with DDX58 (via CARD domain). Interacts (via coiled coil) with influenza A virus NS1 protein; this interaction specifically inhibits TRIM25 multimerization and TRIM25-mediated DDX58 CARD ubiquitination, thereby suppressing DDX58 signal transduction.
INTERACTION: P03496:NS (xeno); NbExp=3; IntAct=EBI-2341129, EBI-2547442;
SUBCELLULAR LOCATION: Cytoplasm. Note=Colocalized with DDX58 at cytoplasmic perinuclear bodies.
INDUCTION: By interferons.
DOMAIN: The RING-type zinc finger is important for ISG15 E3 ligase activity and autoISGylation. AutoISGylation negatively regulates ISG15 E3 ligase activity.
DOMAIN: The C-terminal B30.2/SPRY domain interacts with the first N-terminal CARD domain of DDX58.
PTM: Auto-ISGylated.
SIMILARITY: Contains 1 B30.2/SPRY domain.
SIMILARITY: Contains 1 RING-type zinc finger.
WEB RESOURCE: Name=Wikipedia; Note=TRIM25 entry; URL="";

-  MalaCards Disease Associations
  MalaCards Gene Search: TRIM25
Diseases sorted by gene-association score: influenza (7), breast cancer (2), pericardial tuberculosis (2), low compliance bladder (1)

-  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: 54.56 RPKM in Whole Blood
Total median expression: 566.44 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 -25.9061-0.425 Picture PostScript Text
3' UTR -1349.703791-0.356 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
IPR001870 - B30.2/SPRY
IPR003879 - Butyrophylin
IPR008985 - ConA-like_lec_gl_sf
IPR006574 - PRY
IPR018355 - SPla/RYanodine_receptor_subgr
IPR003877 - SPRY_rcpt
IPR001841 - Znf_RING
IPR017907 - Znf_RING_CS

Pfam Domains:
PF00622 - SPRY domain

ModBase Predicted Comparative 3D Structure on Q14258
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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 BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003723 RNA binding
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016740 transferase activity
GO:0016874 ligase activity
GO:0045296 cadherin binding
GO:0046872 metal ion binding
GO:0061630 ubiquitin protein ligase activity

Biological Process:
GO:0002376 immune system process
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0006513 protein monoubiquitination
GO:0016032 viral process
GO:0016567 protein ubiquitination
GO:0019985 translesion synthesis
GO:0030433 ER-associated ubiquitin-dependent protein catabolic process
GO:0032480 negative regulation of type I interferon production
GO:0033280 response to vitamin D
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043627 response to estrogen
GO:0045087 innate immune response
GO:0046596 regulation of viral entry into host cell
GO:0046597 negative regulation of viral entry into host cell
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051607 defense response to virus
GO:0060333 interferon-gamma-mediated signaling pathway
GO:1902186 regulation of viral release from host cell
GO:1902187 negative regulation of viral release from host cell
GO:1990830 cellular response to leukemia inhibitory factor

Cellular Component:
GO:0005622 intracellular
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016604 nuclear body

-  Descriptions from all associated GenBank mRNAs
  BX538220 - Homo sapiens mRNA; cDNA DKFZp686D24130 (from clone DKFZp686D24130).
LF384795 - JP 2014500723-A/192298: Polycomb-Associated Non-Coding RNAs.
MA620372 - JP 2018138019-A/192298: Polycomb-Associated Non-Coding RNAs.
LF209253 - JP 2014500723-A/16756: Polycomb-Associated Non-Coding RNAs.
MA444830 - JP 2018138019-A/16756: Polycomb-Associated Non-Coding RNAs.
BC053605 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone IMAGE:6008783).
AK024597 - Homo sapiens cDNA: FLJ20944 fis, clone ADSE01780.
BC013752 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone IMAGE:4525015), with apparent retained intron.
LF327291 - JP 2014500723-A/134794: Polycomb-Associated Non-Coding RNAs.
MA562868 - JP 2018138019-A/134794: Polycomb-Associated Non-Coding RNAs.
BC038247 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone IMAGE:4524805).
LF327290 - JP 2014500723-A/134793: Polycomb-Associated Non-Coding RNAs.
MA562867 - JP 2018138019-A/134793: Polycomb-Associated Non-Coding RNAs.
JD023393 - Sequence 4417 from Patent EP1572962.
JD035472 - Sequence 16496 from Patent EP1572962.
JD034831 - Sequence 15855 from Patent EP1572962.
DL492324 - Novel nucleic acids.
DL490814 - Novel nucleic acids.
AB208994 - Homo sapiens mRNA for tripartite motif-containing 25 variant protein.
BC016924 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone MGC:21231 IMAGE:4419084), complete cds.
BC042541 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone MGC:17069 IMAGE:4338818), complete cds.
HZ409099 - JP 2015528002-A/1696: CHIRAL CONTROL.
LG052433 - KR 1020150036642-A/1699: CHIRAL CONTROL.
D21205 - Homo sapiens efp mRNA for estrogen responsive finger protein, complete cds.
LF327289 - JP 2014500723-A/134792: Polycomb-Associated Non-Coding RNAs.
MA562866 - JP 2018138019-A/134792: Polycomb-Associated Non-Coding RNAs.
HZ480257 - JP 2015535430-A/763: TERMINALLY MODIFIED RNA.
JC512920 - Sequence 3173 from Patent WO2014113089.
LF161889 - JP 2016513950-A/1955: Oligomers with improved off-target profile.
LQ070508 - Sequence 832 from Patent EP2964234.
MA731893 - JP 2017140048-A/763: TERMINALLY MODIFIED RNA.
FR772788 - Homo sapiens microRNA hsa-miR-3614-3p.
JD328166 - Sequence 309190 from Patent EP1572962.
HZ480258 - JP 2015535430-A/764: TERMINALLY MODIFIED RNA.
JC512921 - Sequence 3174 from Patent WO2014113089.
LF160521 - JP 2016513950-A/587: Oligomers with improved off-target profile.
LQ070509 - Sequence 833 from Patent EP2964234.
LQ724871 - Sequence 504 from Patent WO2018096084.
LY486545 - KR 1020170014835-A/3: Genetic marker for predicting and detecting development of colorectal cancer.
MA405804 - WO 2018155427-A/578: A probe with reduced false positive binding, a method to desing the probe, and the use thereof.
MA731894 - JP 2017140048-A/764: TERMINALLY MODIFIED RNA.
FR772789 - Homo sapiens microRNA hsa-miR-3614-5p.
JD474362 - Sequence 455386 from Patent EP1572962.
JD465576 - Sequence 446600 from Patent EP1572962.
JD525218 - Sequence 506242 from Patent EP1572962.
JD305026 - Sequence 286050 from Patent EP1572962.
LF327288 - JP 2014500723-A/134791: Polycomb-Associated Non-Coding RNAs.
MA562865 - JP 2018138019-A/134791: Polycomb-Associated Non-Coding RNAs.
JD477936 - Sequence 458960 from Patent EP1572962.
JD278236 - Sequence 259260 from Patent EP1572962.
JD446170 - Sequence 427194 from Patent EP1572962.
JD096258 - Sequence 77282 from Patent EP1572962.
AK310720 - Homo sapiens cDNA, FLJ17762.
JD422765 - Sequence 403789 from Patent EP1572962.
JD466961 - Sequence 447985 from Patent EP1572962.
AB384815 - Synthetic construct DNA, clone: pF1KB3493, Homo sapiens TRIM25 gene for tripartite motif-containing protein 25, complete cds, without stop codon, in Flexi system.
LF327283 - JP 2014500723-A/134786: Polycomb-Associated Non-Coding RNAs.
MA562860 - JP 2018138019-A/134786: Polycomb-Associated Non-Coding RNAs.
LF327282 - JP 2014500723-A/134785: Polycomb-Associated Non-Coding RNAs.
MA562859 - JP 2018138019-A/134785: Polycomb-Associated Non-Coding RNAs.
LF327281 - JP 2014500723-A/134784: Polycomb-Associated Non-Coding RNAs.
MA562858 - JP 2018138019-A/134784: Polycomb-Associated Non-Coding RNAs.
LF327280 - JP 2014500723-A/134783: Polycomb-Associated Non-Coding RNAs.
MA562857 - JP 2018138019-A/134783: Polycomb-Associated Non-Coding RNAs.
MB407069 - WO 2019159884-A/559: Kit, device, and method for detection of dementia.
MB406671 - WO 2019159884-A/161: Kit, device, and method for detection of dementia.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04622 - RIG-I-like receptor signaling pathway

BioCarta from NCI Cancer Genome Anatomy Project
h_EfpPathway - Estrogen-responsive protein Efp controls cell cycle and breast tumors growth

Reactome (by CSHL, EBI, and GO)

Protein Q14258 (Reactome details) participates in the following event(s):

R-HSA-918224 DDX58 is K63 polyubiquitinated
R-HSA-1169403 Interaction of E3 ligase with ISG15:E2 complex
R-HSA-1169394 ISGylation of IRF3
R-HSA-1169395 ISGylation of viral protein NS1
R-HSA-1169398 ISGylation of host protein filamin B
R-HSA-1169402 ISGylation of E2 conjugating enzymes
R-HSA-1169405 ISGylation of protein phosphatase 1 beta (PP2CB)
R-HSA-1169406 ISGylation of host proteins
R-HSA-5653756 TRIM25 binds monoUb:164-PCNA
R-HSA-5653754 UBE2L6:TRIM25 ISGylates monoUb:K164-PCNA
R-HSA-1678843 ISGylation of protein translation regulator 4EHP
R-HSA-168909 viral dsRNA:IFIH1, viral dsRNA:K63polyUb-DDX58 bind MAVS
R-HSA-936378 Inhibition of DDX58/IFIH1 signaling by ATG5:ATG12:MAVS
R-HSA-937343 NLRC5 interacts with DDX58/IFIH1
R-HSA-1678842 Competitive inhibition of translation initiation by ISGylated 4EHP
R-HSA-168934 MAVS interacts with RIPK1 and FADD
R-HSA-918227 Recruitment of TRAF3 to MAVS
R-HSA-918230 Recruitment of TRAF6/TRAF2 to IPS-1
R-HSA-990528 Interaction of PCBP2 with MAVS
R-HSA-933528 Interaction of MEKK1 with TRAF6
R-HSA-933537 Recruitment of TANK to TRAF6
R-HSA-933539 Recruitment of IKK complex
R-HSA-918225 TBK1/IKK epsilon complex interacts with MAVS bound TRAF3
R-HSA-936381 OTUD5 deubiquitinates TRAF3
R-HSA-933526 Recruitment of caspase-8 and -10 to FADD complex
R-HSA-990526 Recruitment of AIP4 and K48 ubiquitination of MAVS/IPS-1
R-HSA-933527 Recruitment of TBK1/IKK epsilon complex to TANK:TRAF6
R-HSA-918232 Recruitment of IRF3,IRF7
R-HSA-918229 Phosphorylation and release of IRF3/IRF7
R-HSA-933523 Dimerzation of procaspase-8, procaspase-10
R-HSA-933538 Recruitment of IRF7 to TRAF6
R-HSA-933525 Phosphorylation and release of IRF7
R-HSA-933530 Activation of IKK by MEKK1
R-HSA-933532 Processing of caspases
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-877300 Interferon gamma signaling
R-HSA-1169408 ISG15 antiviral mechanism
R-HSA-5656169 Termination of translesion DNA synthesis
R-HSA-168249 Innate Immune System
R-HSA-913531 Interferon Signaling
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes
R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
R-HSA-168256 Immune System
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-73893 DNA Damage Bypass
R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
R-HSA-918233 TRAF3-dependent IRF activation pathway
R-HSA-933541 TRAF6 mediated IRF7 activation
R-HSA-933542 TRAF6 mediated NF-kB activation
R-HSA-73894 DNA Repair
R-HSA-5689896 Ovarian tumor domain proteases
R-HSA-5688426 Deubiquitination
R-HSA-597592 Post-translational protein modification
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: EFP, NM_005082, Q14258, RNF147, TRI25_HUMAN, uc002iut.1, uc002iut.2, uc002iut.3, uc002iut.4, uc002iut.5, ZNF147
UCSC ID: uc002iut.5
RefSeq Accession: NM_005082
Protein: Q14258 (aka TRI25_HUMAN or Z147_HUMAN)
CCDS: CCDS11591.1

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